Gen info
- Nerium oleander is a shrub or small tree cultivated worldwide in temperate and subtropical areas and as ornamental or landscaping plant. It is the only species currently classified in the genus Nerium, belonging to the subfamily Apocynoideae of the dogbane family Apocynaceae. So widely cultivated, no precise region of origin has been identified. (18)
- The taxonomic name Nerium oleander was first assigned by Linnaeus in 1753.
- Etymology: The genus name Nerium is the Latinized form of the Ancient Greek name for the plant nerion, which derived from Greek word for water, neros, referring to the natural habitat of oleander along rivers and streams. The origin of the species epithet oleander is disputed. One suggestion is that it is a Latinized form of the Greek compound noun: ollyo 'I kill" and the Greek noun for man, aner, referring to oleander's toxicity to humans. (18)

Botany
Adelfa is an erect, smooth shrub, 1.5 to 3 meters high with a cream-colored, sticky, resinous juice. Leaves are in whorls of 3 or 4, linear-lanceolate, 10 to15 centimeters long, with numerous horizontal nerves. Flowers are showy, sweet-scented, single or double, 4 to 5 centimeters in diameter, white, pink, or red, borne on terminal inflorescences (cymes). Fruit is cylindric, paired, with deep linear striations, 15 to 20 centimeters long. Seeds are numerous and compressed, with a tuft of fine, shining, white and grayish, silky hairs.

Distribution
- Introduced by the Spaniards.
- Throughout the Philippines in cultivation.
- Nowhere established.
- Native to Afghanistan, Albania, Algeria, Baleares, Corse, Cyprus, East Aegean Is., France, Greece, Gulf States, India, Iran, Iraq, Italy, Lebanon-Syria, Libya, Morocco, Myanmar, Niger, Oman, Pakistan, Palestine, Portugal, Sardegna, Sicilia, Spain, Tunisia, Turkey, Turkey-in-Europe, West Himalaya, Yugoslavia. (41)
- Now pantropic.

Constituents
- Phytochemical screening of plant materials yielded alkaloids, tannins, flavonoids, amino acids, phenols, terpenoids, carbohydrates, loco anthocyanidine, steroids, and glycosides. (33)
- Study yielded glycoside, oleandrin; tannin; volatile oil, 0.25%.
- Yielded two principles: neriin and oleandrin, glucosides with properties similar to digitalin.
- The seeds yield fat 17.4%, phytosterin and l-strophanthin.
- Bark contains toxic glycosides: rosaginin and nerlin, volatile oil, fixed oil.
- Nerium odorum's bark yielded two toxic bitter principles–neriodorin and neriodorein. Another toxic principle is karabin. Both karabin and neriodorin are probably resins, rather than glucosides.
- Roots yield a yellow, poisonous resin, tannic acid, wax, and sugar, but no alkaloid or volatile poison.
- Study isolated 14 compounds: a new pregnane, 14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid (16β,17α), and thirteen known cardiac glycosides:oleandrin, oleandrigenin, neriosid, nerigoside,16,17-didehydrosomalin, oleaside A, adynerin, odoroside-A , 3β-hydroxy-5β-carda-8β,14β,20,(22)-trienolid, odoroside H, deacetyloandrin, adynerigenin,3β-hydroxy-5α-8β,14β-epoxy-card-20(22)-enolid.
- Study of roots yielded carbohydrates, proteins, steroids, flavanoids, tannins, and phenolic compounds.
- GC-MS analysis of leave extract for alkaloid constitution yielded 8 alkaloid compounds: 2-cyclopenten-1-one, 2-hydroxy-3-methyl (1), 5-Hydrooxy methylfurfural (2), β-d-allopyranoside, methyle 6-dioxy-2-o methyl (3), 2-Cyclohexen-1-one, 4-(hydroxybutyle)-3.5.5- trimethyl (4), 3-Eicosene (5), 1-Monolinoleoyl-glycerol trimethylsilyl ether (6), 9.12.15-Octadecatrienoic acid,2,3bis[trimethylsilyl]oxy] propyl ester (7), and Octadecane, 3-ethyl-5-(2-ethylbutyl) (8). (56)
- Plant yielded a number a related cardiac glycosides similar in activity to digitalis. Main glycosides are oleandrin, neriin, cardenolides, bentiobiosyl, oleandrin and odoroside. Plant has yielded other pharmacologically active compounds, including folinerin, rosagenin, rutin, and oleandomycin. (59)
- Study of N. oleander yielded three new pregananes, 21-hydroxypregna-4,6-diene-3,12,20-trione (1), 20R-hydroxypregna-4,6-diene-3,12-dione (2), and 16β,17β-epoxy-12β-hydroxypregna-4,6-diene-3,20-dione (3), along with two known compounds, neridienone A (4) and neridienone B (5). (see study below) (62)
- Phytochemical screening of flower extracts yielded alkaloids, flavonoids, proteins, tannins, saponins, sterols, carbohydrates, and phenols, with absence of quinones. (see study below) (64)
- Phytochemical screening of ethanol, hot water, and cold water extracts of leaves yielded alkaloids, phenols, cardiac glycosides, flavonoids, saponins, terpenes, tannins, ratenges, coumarins, essential oil, with absence of steroids. (see study below) (77)
- GC-MS analysis of flower essential oil recorded 64 components accounting for 94.69% of total essential oil. Total phenolics was 136.54 mg gallic acid/g essential oil. (see study below) (80)

Toxicity
- While an important medicinal plant in Indian folk medicine, it is a potentially lethal plant with many causes of accidental poisoning in tropical and subtropical parts of the world, as well as reports on ts use for suicide in South Asian countries, especially India and Sri Lanka. (59)
- All parts of the plant are considered toxic and can poison livestock and humans. Ingestion of the plant can cause cardiac, gastrointestinal, and central nervous system effects.
- Two toxic cardiac glycosides (cardenolides) oleandrin and neriin have been isolated from plant parts, reported as positive inotropic, negative chronotropic, cross reactive, and similar to the toxin in foxglove (Digitalis). (60)
- The pharmacologic actions of of neriin and oleandrin resemble those of digitalis glucosides. In human beings, toxicity manifests as nausea, vomiting, colic, decreased appetite, dizziness, drowsiness, bradycardia and irregular heart beats, pupillary dilation, and sometimes unconsciousness attributed to digitalis poisoning.
- Some invertebrates are reportedly unaffected by oleander toxins and can feed on the plants. Caterpillars of the polka-dot wasp moth specifically feed on oleanders, eating only the pulp surrounding the leaf-veins. (59)
- Despite its toxicity, oleander is of great medical importance and used for heart conditions, asthma, epilepsy, cancer, dysmenorrhea, leprosy, malaria, ringworm, among others. (59)
- In cattle and horse, as little as 0.005% body weight of green leaves is reportedly lethal. (69)
- Oleander leaves administered via NGT at 40 mg/kbw reported to cause severe gastrointestinal and cardiac toxicosis. (69)
- Is Nerium a toxin, snake oil, or an anti-aging marvel? (73)
- The raw plant from which Anvirzel (TM) is extracted is highly toxic and consumption may be fatal. (see study below) (55)
- Toxicity Effects / A Comprehensive Review: The review reports on the potential side effects of all fresh and dried plant parts on animals and humans. the poisoning effects of plant parts or their active alkaloids induced infiltration of cells with hemorrhage and severe negative changes in the lung, induced lesions and infiltration of inflammatory cells into portal spaces with scattered necrosis of hepatocytes n the liver, and varying degrees of cardiac toxicity including hemorrhage, myocardial degeneration, and necrosis, along with EKG findings of arrhythmias, sinus bradycardia and prolonged P-R intervals. The toxic effects are mostly related to its inhibitory effects on the Na+K+ATPase pump in the cellular membrane. However, the exact molecular mechanism of toxicity remain unclear. (75)
• Arrhythmogenic Activity / Leaves: (see study below) (84)

Properties
- Leaves and flowers are considered cardiotonic, diaphoretic, diuretic, emetic and expectorant.
- Whole plant believed to have anticancer, anti-inflammatory, antibacterial, sedating, and anthelmintic effects.
- Reported biologic activities to include anti-inflammatory, sedative, anti-bacterial, cardiac, anti-neoplastic and anthelmintic.
- Studies have suggested mollusicidal, cardioprotective, neuroprotective,  analgesic, larvcidal, antibacterial, antifungal, anti-angiogenesis, cytotoxicity, anticancer, hepatoprotective, antidiabetic, anticonvulsant, antioxidant, antihyperlipidemic, anti-inflammatory, anthelmintic, toxicity, CNS depressant, cardiotonic, repellant, antiulcer, analgesic, anti-arthritic, antianxiety, antiviral, anti-polio virus properties.

Parts used
Bark. flowers, leaves, fruits.

Uses
Folkloric
- Herpes zoster (skin): Crush leaves, mix with oil and apply on lesions. Do not apply on raw surface. Milky juice of the plant is irritating. Caution: Not to be taken internally.
- Herpes simplex: Mix 1 cup of chopped leaves and bark with 2 tablespoons of oil. Apply to lesions 3 times daily.
- Ringworm: Chop a foot long branch and mix with 1 cup chopped fresh young leaves. Mix the juice with 5 drops of fresh coconut oil. Apply 3 times daily.
- Snake bites: Pound 10 leaves and a piece of branch. Apply poultice to the wound.
- Root used, locally and internally, by women in western and southern India and in the central Malay Peninsula for suicide and for procuring criminal abortion.
- Past of bark of the roots is applied externally for ringworm.
- Used in leprosy, skin eruptions, and boils.
- In the Punjab and Cashmere areas, roots are used for asthma.
- Leaves used in the treatment of malaria and dysmenorrhea; also used as abortifacient.
- Roots, made into paste with water, used for hemorrhoids.
- Leaves and bark used externally for eczema, snake bites and as insecticide; internally, used for epilepsy.
- Dried leaves used as sternutatory.
- Infusion of leaves and fruit used a cardiac regulator.
- In Morocco, fresh leaves applied to tumors to hasten suppuration.
- In traditional Chinese medicine, the flowers and leaves have been used to stimulate the cardiac muscles, relieve pain and eliminate blood stasis.
Others
- Skin care: Formulated as age-defying skin care product.

Studies
• Molluscicidal activity / Bark: Study evaluated the molluscicidal activity of N. indicum bark against Lymnaea acuminata. Toxicity of different bark preparations was both time and dose dependent. (31) Study showed the bark of Nerium indicum as an important source of botanical molluscicide and is an effective insecticide against Blatta orientalis. Glycosides, steroids and terpenoids were also isolated from Nerium indicum.
• Primary Metabolites: Study on the quantification of primary metabolites in N. indicum yielded carbohydrates, proteins, phenols, lipids, etc. N. indicum's stem contains higher levels of phenol which has immuno-modulating, anti-tumor and antibacterial activities. (1)
• Cardiovascular Effect / Tincture: Tincture Karveer is a potent cardiotonic drug which is also purported to relieve symptoms of cor pulmonale as a bronchodilator and cough sedative. The tincture is considered safe and helpful, and promising for the treatment of CHF in humans. (2)
• Neuroprotective / Polysaccharides / Flowers: Study of isolated polysaccharides from the flowers of N. indicum (J6) showed potential as a neuroprotective agent against neuronal death in Alzheimer's disease through a mechanism that may primarily rely on inactivation of the JNK signaling pathway. (3)
• Polysaccharides / Nerve Growth Factor-like Effect: Study of polysaccharides J1 (a rhamnogalacturonan) and J2 (a xyloglucan) from the whole flowers of N. indicum were tested on the proliferation and differentiation of PC12 pheochromocytoma cells and found to have nerve growth factor-life effect. (4)
• Analgesic: Study of extract of flowers and roots of N. indicum showed promising antinociceptive activity mediated through the prostaglandin pathways with analgesic principles interfering with the biosynthesis of prostaglandins. (5)
• Larvicidal: Study of larvicidal lethality of extracts of lattices of N indicum and E royleana on Culex quinquefasciatus showed significant delay in embryonic development of Culex larvae. (6)
• Antimicrobial / Antifungal / Dried Leaves: In a study of the ethanolic extracts of dried leaves of N. indicum and Martynia annua, N indicum showed significant antibacterial and antifungal activity compared to M. annua. (7)
• Anti-Angiogenesis: Study yielded three oligosaccharides. Bioactivity angiogenesis testing showed two of the oligosaccharides significantly inhibited the HMEC-1 cell tube formation. (8)
• Cytotoxicity / Anticancer: Most of the compounds isolated from the leaves of N. indicum exhibited strong cytotoxicity against HeLa cell. Odoroside-A exhibited the strongest cytotoxicity. (9)
• Molluscicidal / Bark: Study of different bark preparations showed varying degrees of time- and dose-dependent molluscicidal activity. (10)
• Anti-Ulcer: Study of a methanol extract against pylorus-induced gastric ulcer and indomethacin-induced ulcer in rats showed significant antiulcer activity in all models with significant reduction of gastric volume, free acidity, and ulcer index. Results suggest an antisecretory effect. (11)
• Anti-Diabetic / Leaves: Study investigated the antidiabetic activity of a leaf extract in alloxan-induced diabetic albino rats. Results showed significant antidiabetic activity which may be due to improvement of the glycemic control mechanisms. (32)
• CNS Effects / Sedative / Hypnotic : Study on behavior pattern in mice showed fractions of leaves extract induced sedation at low dose and hypnosis at high doses. Fractions also showed significant decrease in locomotion counts, decrease in motor performances and enhancement of hexobarbital sleeping time. Effects are possibly through GABA-ergic modifications. (12)
• Anti-HIV / Anticancer: In a small clinical trial (20 patients in a DB, placebo controlled study) in a Johannesburg AIDS clinic evaluating the effectiveness of supplements ingredients (Nerium oleander and Sutherlandia frutescens) against HIV results showed significant improvement with an increase in CD4 count while the placebo group declined. (14)
• Hepatoprotective / CCl4-Induced Liver Injury: A methanolic plant extract showed remarkable hepatoprotective activity against carbon-tetrachloride induced hepatotoxicity in rats. (15) Study showed antioxidant and hepatoprotective activity of methanol flower extract on CCl4-induced hepatotoxicity. (40)
• Toxicity Studies: Study evaluated the toxic effects of a crude watery extract in male adult guinea pigs. The lowest nonlethal dose was 300 mg/kbw and doses of 450 to 900 caused varying frequency of mortality. The LD50 is 540 mg/kbw. (16)
• Toxicity Studies / Experimental Poisoning in Sheep: Study reported clinical, ECG, and pathologic findings in goats consistent with those reported in sheep and cattle. Main signs were related to the gastrointestinal and cardiovascular systems. Study concludes goat is susceptible to oleander toxicosis just like other domestic ruminants. However, the unpalatable nature of the plant and the selective feeding habit of the goat, make poisoning in this species infrequent. (17)
• Anvirzel / Antitumor / Anticancer: Study evaluated the cell killing effects of Anvirzel, an extract of oleander, and Oleandrin, a derivative compound, on human, canine, and murine tumor cells. Both Anvirzel and Oleandrine were able to induce cell killing in human cancer cells, but not in murine cancer cells. The cell-killing potential of Oleandrin was greater than that of Anvirzel. Results conclude both act in a species-specific manner. (20)
• CNS Activities / Anticonvulsant / Flower Extract: Study evaluated the CNS activity of a 50% hydroalcoholic flower extract in mice. Results showed significant reduction of spontaneous motor activity, potentiation of pentobarbital-induced sleep, and protection against electroshock-induced convulsions. (21)
• Antidiabetic / Leaf Extract: Study investigated the antidiabetic effect of a leaf extract in alloxan induced diabetic albino rats. The extract showed significant antidiabetic activity and prevented weight loss in diabetic rats. The antihyperglycemic action may be due to improvement of glycemic control mechanisms. Standard used was glibenclamide. (22)
• Anti-Inflammatory / Leaf Extract: Study of various leaf extracts of Nerium oleander showed significant anti-inflammatory and antipyretic activity. The antipyretic effect was almost equivalent to paracetamol. (23)
• Antioxidant / Phenolic Content: Study evaluated various extracts of N. oleander for antioxidant using various assays and total phenolic content. Methanolic and aqueous methanolic extracts showed the highest amount of total phenolic content. Results showed flowers can be a potential source of natural antioxidants. (24)
• Toxicity / Seed Extract / Rodenticide: Study evaluated to basic toxicity of seed extract of Indian oleander on the bandicoot rat, Bandicota bengalensis in the laboratory. Results showed the seed extract can be used as an effective bio-rodenticide with suitable bait bases. (25)
• Biomonitoring of Lead Pollution: Study examined the concentration of Pb, Cd, and Cu in leaves of N. oleander and Robinia pseudoacacia plants in biomonitoring of atmospheric pollution. Results showed Nerium oleander can be used for biomonitoring of Pb. (26)
• Antibacterial / Antioxidant / Cytotoxicity / Leaves and Flowers: Study showed methanol extracts to have high antioxidant activity on DPPH assay. Trichloromethane and methanol extracts showed strong antibacterial activity. The dichloromethane extract showed high cytotoxic effects against T47D, HepG-2 and K562 cell lines. (27)
• Antihyperlipidemic / Flowers: Study evaluated the toxicity profile of 50% hydroethanolic extracts of flowers using brine shrimp lethality assay and MTT cytotoxicity assay. Results showed no toxicity with a wide safety margin and a significant ameliorative action on elevated lipids and lipoproteins in a dose-dependent manner. (28)
• Antibacterial / Leaves: Study evaluated the antibacterial potential of Nerium indicum leaves. Results showed a benzene extract to be more effective than an ethanolic extract in inhibition of Bacillus subtilis. Standard used was Ofloxacin. Both extracts showed negligible activity against E. coli. Phytochemical screening yielded cardiac glycosides, tannins and phenolic compounds, alkaloids, and flavonoids. (29) Study evaluated various extracts of N. oleander for antimicrobial effect and MIC against B. subtilis, S. lutea, E. coli, and K. pneumonia. A petroleum ether extract inhibited the growth of all tested bacteria. Highest inhibition was against E. coli (1.0 cm) with MIC of 2 µg/ml. (58)
• Anthelmintic / Roots: Study evaluated various extracts for anthelmintic activity against adult Indian earthworm, Pheretima posthuma. The ethanolic extract was more active, demonstrating paralysis and death of worms in less time compared to the other extracts and albendazole at higher concentrations. (30)
• Toxicity / Cardiac Glycosides / Oleandrin & Oleandrigenin: Considered a poisonous plant because of compounds that exhibit toxicity, especially in animals, when consumed in excessive amounts, for example, the cardiac glycosides oleandrin and oleandrigenin. However, despite "poisonous" designation, there are very few reports of toxicity in humans. In 2002 there were 842 human exposures reported in the U.S., with only 3 reported deaths from 1985 through 2005. Fatalities were associated with ingestion; no toxicity or deaths have been reported from contact or topical administration. (33)
• Antibacterial / Anticancer: Extracts of N. oleander showed antibacterial activity with inhibition of pathogenic bacteria E. coli and Staphylococcus aureus. It anti-cancer activity compared with anticancer drug cisplatin on the growth of (L20B) cell line. (33)
• Larvicidal / Flowers / Culex quinquefasciatus: Study of crude hexane and aqueous extract of Nerium oleander flowers showed larvicidal activity against filarial vector, Culex quinquefasciatus. Studies are needed to identify the active ingredients responsible for the larvicidal activity. (34)
• CNS Depressant Activity: Study investigated various extract of leaves of N. oleander on CNS activity in rat and mouse. Extracts showed CNS depressant activity with a significant reduction in spontaneous activity, exploration, muscle relaxant activity and significantly potentiated phenobarbitone sodium-induced sleeping time. (35)
• Cardiotonic / Leaf: Study investigated the cardiotonic activity of hydroalcoholic leaf extract of Nerium indicum. Results showed dose dependent positive ionotropic effect on perfused hypodynamic frog heart and isolated rabbit heart. (36)
• Toxicity / Repellent / Larvicidal: Diet based on Nerium oleander leaves halted the development of fourth instar larvae of the desert locust Schistocerca gregaria larvae. Weight loss was due to low food intake related to the repellent and anti-palatable effect of the plant. The toxic effect of N. oleander could be due to toxic secondary compounds contained in the leaves. (37)
• Polysaccharide J6 / Neuroprotective / Flowers: Polysaccharide J6 isolated from the flowers of N. indicum can serve as neuroprotective agent against neuronal death in Alzheimer's disease. The neuroprotective mechanism may rely on the inactivation of JNK signaling pathway. (38)
• Antiulcer / Flowers: Study of flowers extract in gastric ulcer model in rats induced by indomethacin and pylorus ligation showed significant antiulcer activity. Cimetidine was used as reference drug. (39)
• Effect on Fat and Glucose Metabolism in T2 Diabetic Rats: In vivo and in vitro studies suggest the considerable beneficial effect of NO distillate in both fat and glucose metabolism in type 2 diabetes rats fed for 2 weeks on a high-fat diet. (42)
• Toxicity / Leaves: Study evaluated N. oleander leaves extract for toxicity in wistar rats. Results showed the leaves extract caused significant effects on experimental animals due to its toxicity. There was significant variations in hematologic parameters. Histopath studies showed changes ranging from noticeable infiltration of inflammatory cells with low level vascular damage to hepatic necrosis, widening of sinusoidal spaces and mild level of vascular damage. (43) Study evaluated the median lethal dose of aqueous leaf extract subcutaneously injected in rabbits. LD50 was 157.37 mg/kbw. (69)
• Analgesic / Anti-Arthritic / Gel Formulation: Study showed Nerium oleander extract (Iranian Delfi  gel) has effective impact on the reduction of pain and knee stiffness and improvement of physical function in patients with knee osteoarthritis. (44)
• Toxicologic Effects / Hematologic Indices and Heart and Lung Tissues / Leaves: Study evaluated the effects N. oleander on hematological parameters and histopathological changes in the heart and lungs of rabbits treated with sub-lethal doses of aqueous leaf extract for over 28 days. Results showed significant increase (p<0.05) in RBC and WBC and Hb concentration, together with a significant decrease (p<0.05) in platelet counts. Microscopic exam showed interstitial pneumonitis and degeneration and necrosis of muscle fibers in the heart. (45)
• Antibacterial / Solvent Extract of Root, Leaf and Stem: Study evaluated the antibacterial activity of crude extracts of N. oleander from root, stem and leaf extracted using polar and nonpolar solvents against Gram-negative (E. coli, K. pneumonia, and A. tumefaciens) and Gram-positive bacteria (S. aureus and B. subtilis). Results showed great antibacterial potential against all five tested pathogens. Range of MIC and MBC was 1.25-0.078 mg/ml and 0.625-0.039 mg/ml, respectively. (46)
• Skeletal Muscle Relaxant / Flowers: Study evaluated the skeletal muscle relaxant activity of aqueous extract of Nerium oleander flowers in Swiss albino rats. Results showed skeletal muscle relaxant activities with the Actophotometer and Rotarod tests showing significant reduction (p<0.05) in motor coordination of tested animals. Diazepam was used as comparison drug. (47)
• Acute Phase Reaction (APR) / Hepatic Damage: Study evaluated the histopathological effects from an injection of leaves extract on noninjured rat liver. Results showed induced sterile muscle abscess from N. oleander may have time-dependent effects and may induced APR resulting in changes in serum hepcidin, ferritin and total iron levels as well as hepatic damage as evidenced by recruitment of hepatic inflammatory cells. (48)
• Mosquito Larvicidal / Culex pipiens: Study evaluated the insecticidal activity of N. oleander ethanol extract on larval stages 3 and 4 of Culex pipiens. Results showed lethal concentrations LC50 and LC90 of 57.57 mg/mL and 166.35 mg/mL, respectively. Results suggest a potential larvicidal and effective natural biocide against mosquito larvae, Cx. pipiens. (49)
• Anti-Cancer Study / Oleandrin / Phase 1 Clinical Trial: Study reports on cases of advanced cancer patients (9 cases of metastatic cancer) taking N. oleander extract in a Phase 1 clinical trial. Oleandrin, a phytochemical constituent of the extract, has multiple anticancer activities including NF-kappaB inhibition and induction of apoptosis. A renal cell patient experienced tumor regression for 12 months on the extract alone; 3 pancreatic cancer patients and a colon cancer patient experienced disease stabilization. Survival time was extended on all patients from 32 months to 11 years. Study showed good clinical outcomes and low toxicity. (50)
• Chronic Toxicity Study / Leaves: Study evaluated the chronic toxicity effect of multiple exposure of rabbits to aqueous leaf extract of N. oleander at dose rate of 10 mg/kbw. After 30 days, clinical manifestations of toxicity included restlessness, crying, pawing, convulsions, polyuria, emaciation, increased heart sound intensity, paralysis and death. Toxicity was attributed to two potent cardiac glycosides, oleandrin and neriin, a strychnine like toxin, and a heart-active cardiac glycosides. Study reported on the hematolgical changes and correlation of the biochemical changes in the chronic toxicity of the aqueous leaf extract. (51)
• Toxicity and Teratogenic Effects / Leaves: Study evaluated a methanolic extract of plant for toxicity and teratogenic effects on chicken embryo as an animal model. Results showed increasing toxicity and mortality with increasing concentration. In low concentrations the extract had negligible toxicity and teratogenic effects which can be used as therapeutic aims. (52)
• Hepatoprotective / Thioacetamide Toxicity / Leaves: Study of aqueous extracts of N. oleander leaves showed significant hepatoprotective activity against thioacetamide induced liver damage in rats. (53)
• Cardioprotective / Antioxidant / Flowers: Study of a hydroalcoholic extract of N. oleander flowers showed cardioprotective activity in an isoproterenol-induced myocardial oxidative stress in an experimental rat model. The cardioprotection was attributed to improvement of the antioxidant defense system during experimental myocardial necrosis. (54)
• Anticancer / Oleandrin / Anvirzel: Many studies have focused on the anticancer activities of oleandrin because of its apoptotic effects in various cancer cell lines. It also increases sensitivity of PC-3 human prostate cells to radiotherapy and reduces gentamycin toxicity. Anvirzel, a hot water extract of the plant developed as treatment for cancer, AIDS, and CHF, consists of a mixture of oleandrin and glycone oleandrigenin. An early study showed safety in humans when injected intramuscularly. Anvirzel is not an approved cancer treatment in the United States. Until more date on efficacy and toxicity are available, it should not be used outside of clinical trials. (55)
• Restorative Effect on Diabetic Neuropathy: Study evaluated the possible role of N. oleander distillate in the treatment of diabetic neuropathy on diabetes-induced electrophysiological alterations in an animal model. With its antioxidant nature, NeOL treatment produced nearly complete restorations of the diabetes-induced alterations. (57)
• Intoxicating Multiorgan Effects / Leaves: Study investigated the histological effects on extrahepatic organs, hepatic iron deposition and gene expression of some iron regulatory proteins in rats after sterile muscle abscess during acute intoxication of NO leaves decoctions. Results showed inherent toxins present in N. oleander can induce acute phase cytokine expression, cause severe changes in organ architecture, marked changes in the regulation of iron regulatory proteins. (60)
• Invention / Anticancer / Leaves: The invention relates to the use of a sterile non-toxic pyrogen free cold extract from leaves of N. oleander as a supplementary medication to cancer chemotherapy, hormone therapy and/or radiotherapy to restore and/or ameliorate the immune system and to decrease the side effects and increase the antitumor effects of chemo- and radiotherapies, particularly in combination with taxol, adriamycin, cisplatin, 5-FU etc., for possible use in various cancers i.e., bladder, kidney, liver, ovary, pancreas, uterus, testicle, vagina, pleuramesotheliomas and Hodgkin's lymphoma.   (61)
• Bioactive Pregnanes / Cytotoxic Against Cancer Lines: Study yielded three new pregnanes (1,2,3) , along with two known compounds (4,5). Compound 4 (neridienone A) showed in vitro anti-inflammatory activity based on inhibition of induction of intercellular adhesion molecule-1 (ICAM-1). Compounds 1-5 were evaluated for cytotoxic activity against four human cancer cell lines. Compound 4 (neridienone A) showed significant cell growth inhibition of VA-13 (malignant tumor cells induced from WI-28: normal human fibroblast cells) and HepG2 cells (human liver tumor cells). Compounds 1, 2, and 5, showed significant calcein accumulation, a measure of its MDR-reversal activity based on the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in each compound. (63)
• Antimicrobial / Antioxidant / Flowers: Study evaluated the antimicrobial and antioxidant properties of flower extract of Nerium oleander. The ethanol extract showed considerable scavenging capacity by DPPH assay and remarkable reducing power. Antimicrobial evaluation showed activity against selected microorganisms, maximum with the ethanol extract zone of inhibition against Pseudomonas aeruginosa (28mm), Salmonella typhi (25mm), Staphylococcus aureus (21mm), Escherichia coli (20mm), and Bacillus subtilis (17mm). The extract showed maximum zones of inhibition against Aspergillus flavus (18mm) and Rhizopus species (18mm). (see constituents above) (64)
• Experimental Oleander Poisoning in Goats / Leaves:Dried oleander leaves at single lethal dose of 110 mg/kbw were administered orally to five native female goats. Clinical toxicosis began to appear in an hour, manifesting as abdominal pain, ruminal atony, tympany, frequent urination, bradycardia, tachycardia, tachyarrhythmia, depression, weakening, convulsive movements, and death at end stage. Histopath study showed cardiomyopathic changes, varying degrees of hemorrhages in internal organs, extensive renal tubular necrosis, scattered necrosis of hepatocytes, etc. All livestock are susceptible to oleander toxicosis, infrequent only because of the unpalatable nature of the plant. Cattle are more prone to eating of leaves. Studies suggest 110 mg/kbw of dried leaves is lethal for ruminants. High doses (250 and 1000 mg/kbw have been used for experimental induction of acute toxicosis. (65)
• Larvicidal / Leaves:Study evaluated crude aqueous extracts of N. oleander leaves for larvicidal activity against Thaumetopoea wilkinsoni, the most important defoliator in the Mediterranean Basin. Larval defoliation of the pest decreases the annual diameter increment of host trees. The aqueous leaf extract exhibited highest larvicidal activity with 3rd and 4th instar mortality with LD50 of 322.50 ppm and 190.00 ppm after 24 and 48 hours respectively. (66)
• Gold Nanoparticles / Anticancer / Catalytic / Stem Bark: Study reports on the green synthesis of stable gold-nanoparticles utilizing phytochemicals (flavonoids, steroids, and other metabolites) from the stem bark of Nerium oleander. The gold NPs showed highly effective apoptosis of MCF-7 breast cancer cells. Study also demonstrated the stabilized AuNPs as a catalyst. (67)
• Antioxidant / Anti-Inflammatory / Anti-Apoptotic / Skin Regenerative / Aloe-Based / Leaves: Study evaluated the effects of Aloe vera-based Nerium oleander extract (NAE-8®) compared to A. vera extract alone (ALOE) and an aqueous extract of N. oleander (AQ-NOE) in relation to dermatologic potential, antioxidant protection, anti-inflammatory effects and cytokine profiles in vitro. Results showed NAE-8®, a novel component of a commercial cosmetic product, exhibited beneficial antioxidant protection in several cellular models, without induction of leukocyte activation and secretion of inflammatory cytokines. The biological efficacy of NAE-8® was unique from both ALOE and AQ-NOE. (70)
• Anti-Anxiety / Flowers:Study evaluated the anti-anxiety effect of various extracts of N. oleander flowers using an EPM model, and diazepam as standard drug. A chloroform and ethyl acetate extract of N. oleander flowers showed significant increases in open arm entries and mean time spent in open arms with the most pronounced effect produced by 25 and 200 mg/kg for CE and EAE, respectively. (72)
• Subacute Toxicity / Oleandrin and Neriin / Leaves: Study evaluated the toxic effects of an ethanolic extract of N. oleander leaf on hematological cardiac, inflammatory and serum biochemical parameters, as well as histopathological changes in the heart. Results showed significant increases in MCV, white blood cell counts, platelet counts, interleukins (IL-1 and IL-6), tumor necrosis factor alpha, C-reactive protein, ALT, LDH, creatine kinase and CK-MB, especially at high doses, along with marked pathological changes in the heart tissue. (74)
• Antimicrobial / Burn Infection Isolates / Leaves: Study evaluated aqueous and ethanol extracts of leaves against gram positive and gram negative bacteria isolated from burns infection culture using broth dilution and disc diffusion method. Ethanol extract showed higher activity than aqueous extract. Highest activity was against Staphylococcus aureus and Klebsiella spp. The plant extracts against gram negative bacteria showed activity in acidic pH only. (see constituents above) (77)
• Antiviral / Anti-Polio Virus: Study evaluated the antiviral activity of hot and cold water extra ct of N. oleander against six different virus ie herpes simplex virus type 1 (HSV-1), polio virus type 1 (Sb-1), vesicular stomatitis virus (VSV), reovirus type-1 (Reo-1), human immunodeficiency virus type-1 (HIV-1), and yellow fever virus (YFV). Results of plaque reduction assay showed both hot and cold extracts of NO inhibited Sb-1 viral infection. The NO exerted its effect after infection period, particularly during the first two hours post infection. (78)
• Anti-Inflammatory / Leaf, Stem, Roots: Study evaluated oleander leaf, stem, and root extracts on phagocytosis and free radical-related activities of murine peritoneal macrophages. Results showed increase in phagocytosis and decrease in myeloperoxidase (MPO) were in the order of leaf > root > stem. Inhibition of cell adhesion, nitric oxide (NO) and elevation of respiratory burst activity was in order of leaf > stem > root. Leaf extract bioactivity was much higher than stem and root extracts. Results showed N. oleander possesses the capacity to modulate macrophage activities attributable to numerous phytochemicals in the extracts. (79)
• Antitumor / Antioxidant / Antimicrobial / Flower Essential Oil: Study evaluated the antioxidant, antimicrobial, and antitumor activities of essential oil extracted from flower of N. oleander. DPPH, ß-carotene/linoleic acid bleaching, and ferric reducing power assays showed significant antioxidant activity compared to synthetic antioxidants (trolox and BHT). Antitumor activity testing by growth inhibition of Ehrlich ascites carcinoma cells showed gradually increasing antitumor activity with increasing oil concentration. Antimicrobial activity by agar disc diffusion technique showed variable degrees of activity against different strains tested with MICs ranging from 125-500 and 250-2000 µg/mL for bacteria and fungi respectively. Toxicity testing of the essential oil in animal model systems using LD50s, GTP activity, LDH, and creatinine levels indicated no adverse effect in all concentration of EO range. (80)
• Inhibition of Glycolysis / Selective Killing of Cancer Cells / Synergism with Cisplatin / Leaves: Study evaluated a hydroalcoholic extract of leaves containing 4.75% cardenolides for cytotoxic activity in A549 lung cancer cells vs MRC5 non-malignant lung fibroblasts. Results showed cytotoxicity of the extract was significantly higher against the cancer cell line, with a potency and selectivity similar to anticancer drug cisplatin. Pretreatment of A549 cells with antioxidants N-acetylcysteine and catalase slightly prevented the cytotoxicity of the extract, suggesting formation of reactive oxygen species (ROS) participates in its cytotoxic activity, although not in a major role. Induction of DNA damage may play a role in the extract's cytotoxicity. The extract induced marked inhibition of glycolysis inhibitor dichloroacetate. There was moderate synergism when NO extract was administered after cisplatin but a moderate antagonism when added before cisplatin. Results support phase II clinical trials. (81)
• Insecticidal / Bactericidal / Leaves: Study evaluated crude ethanolic extracts of NO leaves for insecticidal and antibacterial activities. Stored grain pest, Trogoderma granarium and fruit fly Drosophila rufa larvae were used as insect models. Results showed N. oleander extract was totally ineffective as contact poison against larvae of T. granarium and D. rufa. At higher doses (100 mg concentration), 10% mortality was observed in T. granarium larvae in both 2nd and 5th instar larvae. In feeding experiments with D. rufa, 10% and 15% mortality of larvae were found after 48 and 72 hours exposure to the leaf extract at  20 mg dose. The extract showed antibacterial activity in all tested gram positive bacterial strains, with remarkable growth inhibition of Bacillus cereus. (82)
• Antidiabetic / Leaves: Study evaluated the antidiabetic effect of a standardized hydromethanolic extract of N. oleander leaves in alloxan induced diabetic mice. The leaf extract demonstrated antihyperglycemic activity by reducing 73.70% blood glucose level after 20 days of treatment. OGTT showed 65.72% reduction in blood glucose after 3h post treatment. There was significant decrease in liver marker enzymes, triglyceride and cholesterol levels. Peroxidase and catalase activities in the liver, kidney, and skeletal muscles were significantly restored along with marked reduction in lipid peroxidation and normalization of hepatic glycogen level. (83)
• Arrhythmogenic Activity / Leaves: Nerium oleander is reported to possess a wide range of pharmacological activities attributed to different glycosides (CG), primarily oleandrin, which can potentially impair the sodium-potassium ATPase (NKA) pump activity and caused inotropic effects on the heart. Study evaluated the potential arrhythmogenic effects of hydroalcoholic extracts of N. oleander leaves in invivo experiments with guinea pigs. The extract elicited severe cardiac arrhythmias that can lead to death with minimal tissue damage. Invitro experiments suggest the extract causes electro-mechanical disturbances in the heart due to inhibition of Na+/K+ pump, mitochondrial swelling, and modulation of sarco(endo)plasmic Ca2+-ATPase. The arrhythmias are mainly associated with impaired cardiomyocyte dysfunction rather than anatomical remodeling and/or autonomic dysfunction. Results revealed potential cardiotoxicity and positive inotropic effect of the extract and an important role in modulation of cardiomyocyte electrophysiology. (84)
• Antiviral Activity / Oleandrin / PBI-06150 / SARS-CoV-2: Study reports an invitro evidence for significant inhibition of SARS-CoV2 by oleandrin and a defined extract of of N. oleander (PBI-06150). Using Vero cells, prophylactic oleandrin (as pure compound or as PBI-06150) at concentrations as low as 0.05 µg/ml exhibited potent antiviral activity against SARS-CoV-2, with 800-fold reduction in virus production, and a 0.1 µg/ml dose resulted in a greater than 3000-fold reduction in infectious virus production. Concentrations of oleandrin up to 10 µg/ml were well tolerated in Vero cells. Study presented evidence of safety and efficacy of defined oleander extract administered to Syrian hamsters in preparation as high as 130 µg/ml of oleandrin. Potent prophylactic and therapeutic antiviral activities demonstrated in the study, along with evidence of safety and efficacy in a hamster model, support further development of oleandrin and/or defined extract containing the molecule for treatment of SARS-CoV-2, associated COVID-19 disease, and reduction of virus spread. (85)

Availability
- Wild-crafted.
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Additional Sources and Suggested Readings
(1)
Quantification of Primary Metabolites of Nerium indicum / Rekha Vijayvergia and Jitendra Kumar / Asian J. Exp. Sci., 2007; Vol 21, No 1: pp 123-128
(2)
A Study of Cardiovascular Effects of Tincture Karveer (Nerium indicum) / V P Trivedi et al / References
Pharmaceutical Biology, 1978; Vol 16, No 4: pp 167-175 / DOI 10.3109/13880207809083268
(3)
New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway / YU Man-Shan et al / Brain research, 2007; Vol 1153: pp 221-230
(4)
Characterization of a Rhamnogalacturonan and a Xyloglucan from Nerium indicum and Their Activities on PC12 Pheochromocytoma Cells / J. Nat. Prod., 2003; 66(1): pp 7–10 / DOI: 10.1021/np020118o
(5)
Analgesic Activity of Methanolic Extracts of Nerium indicum Mill. / Shafi Uddin Ahmed / Dhaka Univ. J. Pharm. Sci., 2006; 5(1-2): pp 85-87
(6)
TOXICITY OF NERIUM INDICUM AND EUPHORBIA ROYLEANA LATTICES AGAINST CULEX QUINQUEFASCIATUS MOSQUITO LARVAE / Nigerian Journal of Natural Products and Medicine, 2003; Vol 7
(7)
Comparative AntiMicrobial studies of Ethanolic extract of leaves of Nerium indicum & Martynia annua / N.P.S. Sengar et al / Department of Pharmacy, Barkatullah University, Bhopal (India), Sagar Institute of Research & Technology, Ayodhya by Pass Road, Bhopal, (India)
(8)
New oligosaccharides prepared by acid hydrolysis of the polysaccharides from Nerium indicum Mill and their anti-angiogenesis activities / Ke Hu et al / Carbohydrate Research, 6 January 2009; Volume 344, Issue 2: pp 198-203 / doi:10.1016/j.carres.2008.10.019
(9)
Studies on Steroids and Cytotoxicity of the Leaves of Nerium Indicum. Mill / Dissertation / Medical Research
(10)
Molluscicidal activity of Nerium indicum bark / Sushma Singh and D.K. Singh / Braz J Med Biol Res, July 1998, Volume 31(7) 951-954 / http://dx.doi.org/10.1590/S0100-879X1998000700011
(11)
ANTIULCER ACTIVITY OF METHANOLIC LEAVES EXTRACT OF NERIUM INDICUM MILL. / Patel Govind, Nayak Satish, Shrivastava Shobhit / IJBR 1(2), 2010, 55-61.
(12)
STUDIES ON THE EFFECT OF THE EXTRACT AND CONSTITUENTS OF NERIUM OLEANDER LEAVES ON THE CENTRAL NERVOUS SYSTEM OF MICE / Atiya Ziaul Haque / Thesis / Pakistan Research Repository
(13)
Clinical Study of Oleander for HIV Is Successful (Oleander Series Part 6) / Tony Isaacs / Natural News
(14)
Determining the effectiveness of an herbal mixture consisting of extracts of Sutherlandia Frutescens and Nerium Oleander on increasing the CD4 cell count of HIV/AIDS patients / Marcus A. Swanepoel / Dissertation 2007
(15)
PROTECTIVE EFFECT OF NERIUM INDICUM ON CCl4 INDUCED HEPATOTOXICITY IN RATS / Govind Patel / INTERNATIONAL JOURNAL OF BIOMEDICAL RESEARCH, Vol 1 No4, 2010 / doi: 10.7439/ijbr.v1i4.68.
(16)
Toxic Effect and Ortal Acute LD50 Study of Nerium oleander in Male Guinea Pigs / M G A Chowdhury et al / Bangl. J. Vet Med, 2004; 2 (2): pp 159-161 / doi: 10.3329/bjvm.v2i2.2562
(17)
Experimental oleander poisoning in goats: a clinical and pathological study / Aslani M R, Movassaghi A R et al / Iranian Journ of Veterinary Research, Vol 8, No 1, Ser. No 18, 2007
(18)
Nerium / Wikipedia
(19)
Nerium oleander / Common names / ZipcodeZoo
(20)
Anvirzel, an extract of Nerium oleander, induces cell death in human but not murine cancer cells. / Pathak S, Multani AS, Narayan S, Kumar V, Newman RA. / / Anticancer Drugs. 2000 Jul;11(6):455-63.
(21)
Some Central Nervous System Activities of Nerium Oleander Linn (Kaner) Flower Extract / KG Singhal, GD Gupta / Tropical Journal of Pharmaceutical Research August 2011; 10 (4): pp 455-461 / http://dx.doi.org/10.4314/tjpr.v10i4.11
(22)
Antidiabetic activity of Nerium indicum leaf extract in alloxan-induced diabetic rats / MS Sikarwar, MB Patil, CK Kokate, S Sharma, V Bhat / PHARMACOLOGY, 2009, Volume 1, No 4, Pp : 330-335 / DOI: 10.4103/0975-1483.59323
(23)
Evaluation of Anti-Inflammatory Activity of Nerium oleander / Senthil Kumar and Ganeshan R Anand / Pharmacia, Vol 1, Issue 1, July 2010
(24)
Antioxidant Activity and Total Phenolic Content of Nerium oleander L. Grown in North of Iran / Maryam Mohadjerani / Iranian Journal of Pharmaceutical Research (2012), 11 (4): 1121-1126
(25)
Toxicity of Nerium indicum Miller seed extract on bandicoot rat, Bandicota bengalensis Gray / K Saravanan*, S Senthilkumar, M Elayaraja & B Suresh / Indian Journal of Experimental Biology ,Vol. 42, October 2004, pp. 1003-1006
(26)
LEAD, CADMIUM AND COPPER CONCENTRATIONS IN LEAVES OF Nerium oleander L. AND Robinia pseudoacacia L. AS BIOMONITORS OF ATMOSPHERIC POLLUTION / Gokce Kaya, Nuh Okumus and Mehmet Yaman* / PSP Volume 19 – No 4a. 2010 Fresenius Environmental Bulletin
(27)
Screening of Biological Activities (Antioxidant, Antibacterial and Antitumor) of Nerium oleander Leaf and Flower Extracts / Pegah Namian, Taravat Talebi, Karimollah Ghasemi Germi* & Fahmideh Shabani / American Journal of Phytomedicine and Clinical Therapeutics, 1(4), 2013, pp 378-384
(28)
Antihyperlipidemic Potential of Polyphenol and Glycoside Rich Nerium oleander Flower against Triton WR-1339-Induced Hyperlipidemia in Experimental Sprague Dawley Rats / V. Gayathri, S. Ananthi, and Hannah R. Vasanthi / Journal of Chemistry, Volume 2013 (2013) / http://dx.doi.org/10.1155/2013/825290
(29)
Phytochemical Screening and Antibacterial Activity of Nerium Indicum Leaves / Doijad C. Rajendra, Pathan B Asma, Suryavanshi S. Jayprakash, Jagtap K. Meena* and Sankpal S. Pournima. / International Journal of Pharmacy Teaching & Practices 2013, Vol.4, Issue 3, 743-746.
(30)
Evaluation of In-vitro Anthelmintic activity of Nerium indicum Mill root extracts. / Rajendra M. Kawade*, Nitin B. Ghiware, Prashant A. Daware, Shrinivas K. Sarje, Mahavir H. Ghante, Sudhir M. Vadvalkar. / Indo American Journal of Pharmaceutical Research, 2013
(31)
Molluscicidal activity of Nerium indicum bark / Sushma Singh and D.K. Singh / Braz J Med Biol Res, July 1998, Volume 31(7) 951-954 / http://dx.doi.org/10.1590/S0100-879X1998000700011
(32)
Antidiabetic Activity of Nerium indicum Leaf Extract in Alloxan-induced Diabetic Rats / Sikarwar, M. S.; Patil, M. B.; Kokate, C. K.; Sharma, S.; Bhat, V. / Journal of Young Pharmacists;2009, Vol. 1 Issue 4, p330
(33)
STUDES ON ANTIBACTERIAL AND ANTICANCER ACTIVITY OF NERIUM OLEANDER EXTRACTS /
Omar Hamad Shehab Al- Obaidi / Eur. Chem. Bull., 2014, 3(3), 259-262.
(34)
Larvicidal activity of Nerium oleander L. (Apocynaceae) flower extracts against Culex quinquefasciatus Say (Diptera: Culicidae) / R. Raveen, K.T. Kamakshi, M. Deepa, S. Arivoli and Samuel Tennyson / International Journal of Mosquito Research, Volume 1 Issue 1 (2014)
(35)
STUDY OF CNS ACTIVITY OF LEAF EXTRACTS OF NERIUM OLEANDER IN EXPERIMENTAL ANIMAL MODELS / SUSANTA KUMAR ROUT*, DURGA MADHAB KAR, BIKRAM ROUT / International Journal of Pharmacy and Pharmaceutical Sciences, Vol 4, Issue 4, 2012
(36)
EVALUATION OF CARDIOTONIC EFFECT OF HYDROALCOHOLIC LEAF EXTRACT OF NERIUM INDICUM: AN ANIMAL STUDY / Sangita Totade* & S.John Premendran / International Journal of Pharmaceutical, Biological and Chemical Sciences (IJPBCS), OCT-DEC 2013, VOL 2, ISSUE 4, pp 20-25
(37)
The toxic effects of Nerium oleander on larvae of the desert locust Schistocerca gregaria (Forskål, 1775) (Ortoptera, Acrididae) / M. BAGARI, A. BOUHAIMI, S. GHAOUT & J. CHIHRANE / Zool. baetica, 24: 193-203, 2013
(38)
New polysaccharide from Nerium indicum protects neurons via stress kinase signaling pathway / Yu MS, Wong AYY, So KF, Fang JN, Yuen WH, Chang RCC / Brain Research, 2007, v. 1153 n. 1, p. 221-230 /
DOI: http://dx.doi.org/10.1016/j.brainres.2007.03.074
(39)
Antiulcer Activity of Nerium indicum in Rats / Patel Govind and Jain Saurabh / Research Journal of Pharmacology 4 (3): 66-68, 2010.
(40)
Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4-induced liver injury in rats / Kumar Gaurav Singhal, Ghanshyam Das Gupta* / Asian Pacific Journal of Tropical Medicine (2012)677-685 / doi: 10.1016/S1995-7645(12)60106-0
(41)
Nerium oleander / Synonyms / KEW: Plants of the World Online
(42)
Nerium oleander Distillate Improves Fat and Glucose Metabolism in High-Fat Diet-Fed Streptozotocin-Induced Diabetic Rats / Ahmet Levent Bas, Sule Demirci,* Nuray Yazihan, Kamil Uney, and Ezgi Ermis Kaya / Int J Endocrinol. 2012; 2012: 947187. / doi: 10.1155/2012/947187
(43)
Clinical and pathological features of Nerium oleanderextract toxicosis in wistar rats / Tasleem Akhtar, Nadeem Sheikh, and Muddasir Hassan Abbasi / BMC Research Notes, 2014; 7(1):947 / DOI: 10.1186/1756-0500-7-947
(44)
A preliminary study on the efficacy of Nerium oleander L. extract on clinical symptoms in patients with knee osteoarthritis / Hosein Soleimani, Mohammad Kamalinejad, Nasroallah Moradi Kor, Seyyed Reza Najafizadeh, Mohammad Askarfarashah*, Nafiseh HoseiniYekta and Seyed SedighehYousefi / European Journal of Experimental Biology, 2014; 4(2): pp 295-298
(45)
Toxic effects of Nerium oleander aqueous leaf extract on haematological parameters and histopathological changes of the lungs and heart in rabbits / Sahar Taheri, Amirali Solati, Pezhman Moradi, Abbas Tavassoly, Jafar Yadi / Comparative Clinical Pathology, November 2013, Volume 22, Issue 6, pp 1189–1193
(46)
Bioactivity of crude extracts of Nerium oleander Linn. extracted in polar and non polar solvents / Meenakshi Fartyal*, Padma Kumar / Journal of Scientific and Innovative Research, 2014; 3(4): pp 426-432
(47)
Evaluation of skeletal muscle relaxant activity of aqueous extract of Nerium oleander flowers in Albino rats / Jayasree Tirumalasatti, Maulik Patel, Ubedulla Shaikh, K Harini, J Shankar / Indian Journal of Pharmacology, 2015; Vol 47, Issue 4: pp 409-413 / DOI: 10.4103/0253-7613.161265
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Effect of Nerium oleander (N.O.) Leaves Extract on Serum hepcidin, Total Iron, and Infiltration of ED1 Positive Cells in Albino Rat / Muddasir Hassan Abbasi, Sana Fatima, Naila Naz, Ihtzaz A. Malik, and Nadeem Sheikh / Hindawi Publishing Corporation BioMed Research International Volume 2013 / http://dx.doi.org/10.1155/2013/125671
(49)
Larvicidal Activity of Nerium oleander against Larvae West Nile Vector Mosquito Culex pipiens (Diptera: Culicidae) / Fouad El-Akhal, Raja Guemmouh, Yassine Ez Zoubi, Abhelhakim El Ouali Lalami / Journal of Parasitology Research, Volume 2015 (2015) / http://dx.doi.org/10.1155/2015/943060
(50)
Abstract 4658: Use of a defined oleander extract by advanced cancer patients: Case reports on toxicity and tumor-related outcomes / Keith I. Block, Charlotte Gyllenhaal and Robert A. Newman / AACR; Cancer Res 2014;74(19 Suppl) / doi:10.1158/1538-7445.AM2014-4658
(51)
Chronic toxicity of Nerium oleander aqueous leaf extract in Rabbits / M. S. Rhaymah, M. I. Al-Farwachi and B. A. Al-Badrani / Al-Anbar J. Vet. Sci., Vol.: 4, Supplement, 2011 / Proceedings of First Medical Conference of Medical Colleges (Veterinary Research): University of Anbar
(52)
The study of toxicity and teratogenic effects of Nerium oleander leave’s extract on chicken embryo / Nasrin Farooghi, Masoud Maleki, Karimollah Ghasemi Germi, Arash Abdolmaleki / New Cellular and Molecular Biotechnology Journal, Vol 5, No 19, July 2015
(53)
Effects of Nerium oleander leaves extract against Thioacetamide induced Liver injury / TASLEEM AKHTAR, NADEEM SHEIKH*, MUDDASIR H. ABBASI, AND AFSHAN S. ABBAS / BIOLOGIA (PAKISTAN) 2014, 60 (1), 37-41
(54)
Cardioprotective Effect of Nerium oleander Flower Against Isoproterenol-Induced Myocardial Oxidative Stress in Experimental Rats / Veeraraghavan Gayathri, MSc, Subhash Ananthi, MSc, Chandranayagam Chandronitha, MSc et al / Journal of Cardiovascular Pharmacology and Therapeutics, Vol 16, Issue 1, 2011
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Oleandrin / Memorial Sloan Kettering Cancer Center
(56)
Alkaloid constitution of Nerium oleander using gas chromatography-mass spectroscopy (GC-MS) / Imad Hadi Hameed*, Huda Jasim, Muhanned Abdulhasan Kareem and Ameera Omran Hussein / Journal of Medicinal Plants Research, March 2015; 9(9):pp 326-334
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Restorative Effect of Distillated Nerium Oleander Extract on Diabetic Neuropathy: Animal Model Study / Sirma Basak Yanardag, Ahmet Akkoca, Figen Çiçek and Murat Ayaz* / Journal of Advanced Neuroscience Research, 2015; 2(2): pp 16-21
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Minimum Inhibitory Concentration Analysis of Nerium oleander against Bacterial Pathogens / M. Abu Hena, Mostofa Jamal, Shahedur Rahman*, Md. Azizul Islam, Md. Rezaul Karim, Md. Samsul Alam, Md. Ziaur Rahman / Asian Pacific Journal of Tropical Biomedicine (2012) S1664-S1666
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NERIUM OLEANDER: IT’S APPLICATION IN BASIC AND APPLIED SCIENCE: A REVIEW / Saabiya Farooqui, Tyulika Tyagi / International Journal of Pharmacy and Pharmaceutical Science, Mar 2018; 10(3) / DOI: 10.22159/ijpps.2018v10i3.22505
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An In Vivo Study on Intoxicating Effects of Nerium oleanderWater Based Extract on Multiorgans of Wistar Rat / Muddasir Hassan Abbasi, Sana Fatima, Muhammad Babar Khawar, Shah Jahan, and Nadeem Sheikh / Canadian Journal of Gastroenterology and Hepatology, Volume 2018, Article ID 4739637 /
https://doi.org/10.1155/2018/4739637
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Invention: Therapeutic use of an extract from the leaves of nerium oleander  / Heinz-Herbert Fiebig, Juay Jamil Rashan, Farid Jamil Rashan / EP Application: EP1976542A1
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Evaluation of antimicrobial efficacy of Flavonoids, Alkaloids and Steroids of Nerium oleander Linn against some pathogenic bacteria / Meenakshi Fartyal, Padma Kumar / Int. J. Drug Dev. & Res., July-September 2014; Vol. 6, Issue 3: pp 119-127
(63)
Bioactive Pregnanes from Nerium oleander / Liming Bai, Liyan Wang, Ming Zhao, Asama Toki, Toshiaki Hasegawa et al / J. Nat. Prod., 2007;  70(1): pp 14–18 / DOI: 10.1021/np068030o
(64)
Antimicrobial and Antioxidant Effects of Nerium oleander Flower Extracts / S. Saranya, D. Archana and K.S. Santhy / Int.J.Curr.Microbiol.App.Sci. 2017; 6(5): pp 1630-1637 / https://doi.org/10.20546/ijcmas.2017.605.178
(65)
Experimental oleander (Nerium oleander) poisoning in goats: a clinical and pathological study / Aslani, M. R.; Movassaghi, A. R.; Janati-Pirouz, H. and Karazma, M. / Iranian Journal of Veterinary Research, University of Shiraz, 2007; Vol 8, No 1, Ser No 18
(66)
Larvicidal activity of Nerium oleander L. leaf extract against Pine Processionary Moth (Thaumetopoea wilkinsoni Tams.) / Gürkan Semiz / Journal of Entomology and Zoology Studies, 2017; 5(6): pp 79-81
(67)
Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity / Abir Chandan Barai, Koushik Paul, Aditi Dey, Subhankar Manna, Somenath Roy, Braja Gopal Bag and Chiradeep Mukhopadhyay / Nano Convergence, 2018; 5:10 / https://doi.org/10.1186/s40580-018-0142-5
(68)
Abstract 4658: Use of a defined oleander extract by advanced cancer patients: Case reports on toxicity and tumor-related outcomes / Keith I. Block, Charlotte Gyllenhaal and Robert A. Newman / Cancer Res 2014; 74(19 Suppl) / doi:10.1158/1538-7445.AM2014-4658
(69)
Acute toxicity of Nerium oleander aqueous leaf extract in rabbits / M. I. Al-Farwachi, M. S. Rhaymah and B. A. Al-Badrani / Iraqi Journal of Veterinary Sciences, 2008; 22(1): pp 1-4
(70)
Antioxidant, anti-inflammatory, anti-apoptotic, and skin regenerative properties of an Aloe vera-based extract of Nerium oleander leaves (NAE-8®) / Kathleen F Benson, Robert A Newman, Gitte S Jensen / DOI https://doi.org/10.2147/CCID.S79871
(71)
STUDIES ON WOOD CHARACTERISTICS USING Nerium oleander L. EXTRACT AS A WOOD BIOPRESERVATIVE / Akshu Chandel / Thesis, 2016
(72)
ANTI-ANXIETY ACTIVITY STUDIES OF VARIOUS EXTRACTS OF NERIUM OLEANDER LINN. FLOWERS / SINGHAL KG, AND GUPTA GD / International Journal of Pharmacy and Pharmaceutical Sciences, 2011; Vol 3, Suppl 4
(73)
Is Nerium a toxin, snake oil, or an anti-aging marvel? / Dr. Jen Gunther / Nov 4, 2013
(74)
Subacute Toxicity of Nerium oleander Ethanolic Extract in Mice / Rania H Abdou, Walaa A Basha and Waleed F Khalil / Toxicological Research, 2019 Jul; 35(3): pp 233–239 / doi: 10.5487/TR.2019.35.3.233 / PMCID: PMC6629440 / PMID: 3134155
(75)
Toxicity effects of Nerium oleander, basic and clinical evidence: A comprehensive review / T Farkhondeh, M Kianmehr, T Kazemi et al / Human & Experimental Toxicology, Jan 2020 / https://doi.org/10.1177/0960327120901571
(76)
Oleandrin is a deadly plant poison, not a COVID-19 cure / The Conversation
(77)
Antimicrobial Activities of Aqueous and Ethanolic Extracts from Nerium oleanderUsed in the treatment of burns infections isolates / Anmar Saadi Aboud / Journal of Pharmaceutical, Chemical, and Biological Sciences, 2015; 2(4): pp 248-258 / ISSN: 2348-7658
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Anti-poliovirus activity of Nerium oleander aqueous extract / Giuseppina Sanna, Silvia Madeddu, Alessandra Serra, David Collu, Thomas Efferth, F Lukmanul Hakkim et al /  Natural Product Research, 2021; 35(4): pp 633-636 / DOI: 10.1080/14786419.2019.1582046
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COMPARATIVE PHYTOCHEMICAL PROFILING AND EFFECTS OF NERIUM OLEANDER EXTRACTS ON THE ACTIVITIES OF MURINE PERITONEAL MACROPHAGES / Priyankar Dey, Tapas Kumar Chaudhuri / Archives of Biological Sciences, 2016; 68(3): pp  515
(80)
Screening of chemical analysis, antioxidant antimicrobial and antitumor activities of essential oil of oleander (Nerium oleander) flower / HFM Ali, FMA El-Ella, NF Nasr / International Journal of Biological Chemistry, 2010; 4(4): pp 190-202 / ISSN: 1819-155X / Record No: 20103151355
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A Hydroalcoholic Extract from the Leaves of Nerium oleander Inhibits Glycolysis and Induces Selective Killing of Lung Cancer Cells / Jose Manuel Calderon-Montaño, Estefania Burgos-Moron, Manuel Luis Orta, Santiago Mateos, Miguel Lopez-Lazaro / Planta Med, 2013;  79(12): pp 1017-1023 /
DOI: 10.1055/s-0032-1328715
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INSECTICIDAL AND BACTERICIDAL EFFECTS OF ETHANOLIC LEAF EXTRACT OF COMMON OLEANDER, NERIUM OLEANDER  / Syed Shahid Ali, Samina Ali, Shahid Munir, Tanzeela Riaz / Punjab Univ J Zool., 2008; 23(1-2): pp 81-90
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Assessment of anti-diabetic activity of an ethnopharmacological plant Nerium oleander through alloxan induced diabetes in mice / Priyankar Dey, Manas Ranjan Saha, Tapas Kumar Chaudhuri et al / Journal of Ethnopharmacology, 2015; Vol 161: pp 128-137 / DOI: 10.1016/j.jep.2014.12.012
(84)
Hydroalcoholic extract from Nerium oleander L. (Apocynaceae) elicits arrhythmogenic activity / Ana Flavia Machado Botelho, Artur Santos-Miranda,  Benito Soto-Blanco, Marilia Martins Melo et al / Journal of Ethnopharmacology, 2017; Vol 206: pp 170-177 / DOI: 10.1016/j.jep.2017.05.031
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Antiviral activity of oleandrin and a defined extract of Nerium oleander against SARS-CoV-2 / Kenneth S Plante, Varun Dwivedi, Jessica A Plante, Diana Fernandez et al / Biomed Pharmacother., 2021; 138:  111457 / DOI: 10.1016/j.biopha.2021.111457 / PMID: 33721754 / PMCID: PMC7927596

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