 Gen info
- Rhododendrons tomentosa is a flowering plant in the family Myrtaceae. The genus was first described in 1841. (3)
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Etymology: The genus name Rhodomyrtus derives from Latin words rhodo meaning 'rose', and myrtus meaning myrtle, referring to the rose-like flowers. The species name tomentosa is Latin, meaning "with flattened hairs", referring to the texture of the leaves. (2)
Botany
• Shrubs, 1-2 m tall. Branchlets grayish tomentose. Leaves opposite; petiole 4-7 mm; leaf blade elliptic to obovate, 3-8 × 1-4 cm, leathery, pubescent when young but glabrescent and shiny with age, abaxially
gray tomentose, secondary veins 1 on each side of
midvein, originating near leaf blade base, and meeting at apex, tertiary veins 4-6 on each side of midvein and connecting midvein to secondary veins, reticulate veins obvious, intramarginal veins 3-4 mm from margin, base broadly cuneate, apex rounded to obtuse and often slightly emarginate or sometimes slightly apiculate. Flowers 1[-3], stipitate, 2-4 cm in diam. Hypanthium obovoid, ca. 6 mm, gray tomentose. Calyx lobes 5, subrounded, 4-5 mm, persistent. Petals 5, violet, obovate, 1.3-2 cm. Stamens red, 7-8 mm. Ovary 3(or 4)-loculed. Style ca. 1 cm. Berry purplish black when mature, urceolate, 1.5-2 × 1-1.5 cm. (Flora of China)
 • An evergreen shrub, up to 3 m tall. Foliage: Opposite, stalked leaves have leaf blades that are oblong, sparsely white woolly below when young, and 2.5-10 by 1.3-4.5 cm, with three distinct longitudinal veins. Flowers: Its 3-4.5 cm wide flowers have magenta pink petals that fade white, and with numerous stamens at the center of the flower, which makes it resemble a cherry blossom. Fruits: Its 1-1.3 cm velvety fruits are oblong, purplish when ripe, with persistent sepals at the tip, and contain many tiny seeds embedded in the purplish pulp. (2)
Distribution
- Native to the Philippines.
- In thickets at low elevation.
- Also native to Borneo, Cambodia, China South-Central, China Southeast, India, Jawa, Laos, Lesser Sunda Is., Malaya, Maluku, Myanmar, Nansei-shoto, Sri Lanka, Sulawesi, Taiwan, Thailand, Vietnam. (1)
- Invasive in some countries, especially Florida, Hawaii, and French Polynesia, spreading to form large, monospecific thickets that displace native flora and fauna. (3)
- In coasts, natural forest, riparian zones, wetlands, moist and wet forests, bog margins, from sea level up to 2400 m elevation. (3)
Constituents
- Phytochemical study yielded terpenoids (Lupeol, β-amyrin, β-amyrenonol, and botulin, 3β-hydroxy-21α-hop-22(29)-en-30-al, Rhodomentones A and B, Tomentosenol A, 4S-focifolidione, and 4R-focifolidione, tomentodione E, Rhodomyrtials A and B, tomentodiones A-M from leaves, and  tomentodiones H-M from roots); phenolics (Rhodomyrtosone A, rhodomyrtosone B, rhodomyrtosone C, and rhodomyrtosone D, 3,3′,4,4′-tetra-O-methylflavellagic acid, rhodomyrtosone I, stigmast-4-en-3-one, rhodomyrtone, rhodomyrtosone D, oleanolic acid, methyl gallate, and 3-O-methylellagic acid 4-O-rhamnopyranoside, tomentosones A and B, rhodomyrtosones G and H, Tomentodiones N-T, Myricetin 3-O-α-L-furanoarabinoside, myricetin 3-O-β-D-glucoside, and myricetin 3-O-α-L-rhamnoside, Rhodomyrtone and piceatonnol 4'-O-ß-D-glucopyranoside, tomentosin, pedunculagin casuariin, and castalagin from leaves), and Watsonianone A from fruits, and Malvidin-3-glucoside, pelargonidin-3,5-biglucoside, delphinidin-3-galactoside, and cyanidin-3-galactoside from flowers); combetrol (phenolics from bark and twigs); Kaempferol 3-O-ß-sambubioside (phenolics from buds), α-pinene, β-pinene, and aromadendrene (lipids from leaves). (4)
- Fruit contains minerals and vitamins: high level of potassium (221.76 mg/150 g fruit),, calcium (73.65 mg), manganese (3.23 mg), iron (1.54 mg), zinc (0.61mg) and copper (0.40 mg). Vitamin C (5.62 mg/150 g fruit) was much lower than other tropical fruits; while vitamin E (3.89 mg/150 g fruit) was higher than mango and avocado.
- Nutrient study of fruit (150g) yielded high levels of dietary fiber (69.94-87.43% of RDA),
α-tocopherol (38.90-51.87%), manganese (≥100%), and copper (44.44%), but low levels of protein (2.63% RDI), lipid (1.59-3.5%), and sugars (5.65%). Predominant fatty acid was linoleic acid (75.36% of total fatty acids)/ Phenolics were high (49.21 mg GAE/g DW) with antioxidant capacity (431.17 µmol Trolox TE/g DW. Piceatannol, a stilbene recently discovered, with potent biological activities, highlights the fruit as a source of health-promoting compounds. (13)
- Study of leaves isolated tomentosenol A (1), along with a pair of epimers, 4S-focifolidione (2) and 4R-focifolidione (3). Compound 1 contained a free syncarpic acid coupled with a terpenoid unit. (see study below) (24)
- Study of leaves isolated 14 compounds including a new acyphloroglucinol, named tomentosone (1), and a new flavonol glycoside, myricetin-3,7,3'-trimethyl ether-5'-O-ß-glucopyranosdie (2), and a known acylphloroglucinol, rhodomyrtone (3). (see study below)
(35)
- Study of leaves isolated a new meroterpenoid, tomentodione E (1), along with four known ones (2-5).
(see study below) (43)
- HPLC-ESI-HR-MS studies on fruit revealed 19 phenolic compounds (PCs), which included stilbenes and elagitannins as major components, followed by anthocyanins, flavonols, and gallic acid. The PCs further quantified by HPLC-DAD, yielded piceatannon, as the major PC in the fruit, with a concentration of 2.3 mg/g dry weight at full maturity stage
- (a concentration 1000-2000 times higher than red grapes, a major source of stilbene in the human diet. (see study below) (45)
- Study of roots isolated two new triterpenoids, tomentoids A and B (1,2), along with five known ones. (see study below) (50)
- Study of aerial parts isolated two new anthracene glycosides, 4,8,9,10-tetrahydroxy-2,3,7-trimethoxy-anthracene-6-O-β-D-glucopyranoside (1) and 2,4,7,8,9,10-hexahydroxy-3-methoxyanthracene -6-O-α-L-rhamnopyranoside (2), along with three known compounds (3-5). (see study below) (54)
- Phytochemical screening of aqueous alcoholic extract of leaves yielded carbohydrates, proteins, aminoacids glycosides, triterpenoids, tannins, and flavonoids. (see study below) (65)
- Study of leaves isolated a new triterpenoid, 2α, 3β, 23α, 29-tetrahydroxyolean-11, 13 (18)-dien-28, 19β-olide, rhodotomoside A (1), along with 6 known triterpenoids (2-7). (see study below) (66)
- Study of CH2Cl2 extract of R. tomentosa leaves isolated two phloroglucinols, tomentosones A and B (1,2). (see study below) (68)
 Properties
- Studies have suggested antimicrobial, bactericidal, antioxidant, antiulcer, anti-inflammatory, anti-candida virulence, immunostimulatory, anticancer, food preservative, antidiabetic, anti-allergic, anti-acne, anti-microbial adherence, anticancer, antidiabetic, antihyperchlesterolemic, antiatherosclerotic, antibiofilm-forming, cell-membrane stabilizing, antidiarrheal, antiviral, anti-quorum sensing, acetylcholinesterase inhibitory, antithrombotic, hepatoprotective, antimycobacterial, haemostatic, antimalarial, anti-hyperpigmentation properties.
Parts used
Fruits, leaves, roots.
 Uses
Edibility
- Fruits are edible; sweet, made into jams, tarts, and pies. In Phu Quoc, Vietnam, fruits are used to make local wine called ruou sim. (2)
Folkloric
- Fruits used for treating diarrhea and dysentery. Crushed leaves used to bandage wounds. Decoction of roots and leaves used for treatment of diarrhea and stomach aches. (2)
- Decoction used as restorative after childbirth. (2)
- In traditional Vietnamese, Chinese and Malaysian medicine, long used for treatment of diarrhea, dysentery, gynecopathy, wound healing, and stomachaches. (4)
- In Indonesia, crushed leaves used for treating wounds. In China, used for treatment of urinary tract infections. In Singapore, use for treatment of pain, heartburn, and snake bites. (4)
- In Thai medicine, used for treatment of coliic, diarrhea, dysentery, abscesses, hemorrhage, and gynecopathy. Also used for formulation of skin-whitening, anti-aging, and skin beautifying agents. (8)
Others
- Cosmetic: Wood tar mixed with coconut shells used for blackening teeth and eyebrows.
- Others: Ornamental cultivation. Also, has shown promise as a fire retardant species for use in fire breaks in the Himalayas. It is fire-adapted, able to resprout prolifically after fire. (3)
Studies
• Potential as Functional Food: Study have showed R. tomentosa with varied nutritional compositions of proteins, amino acids, carbohydrates, lipids, fatty acids, minerals, and vitamins; a promising souurce of biologically active metabolites including phenolic and terpenoid compounds, with invivo and invitro studies suggesting various health benefits i.e., antioxidant, antibacterial, anti-inflammatory, anticancer activities. (see constituents above) (4)
• Antimicrobial / Antioxidant / Leaves, Stems and Fruits: Study showed the ability of leaves, fruits, and stem fractions to scavenge DPPH radicals. The fractions showed highest antioxidant activity compared to partition extracts. Leaves fractions, LM2, LM3,and LM4 showed strong inhibition against E. coli and S. aureus, as well as strong DPPH scavenging activity. From fruits and stem fractions, FM2 and SM1 showed strong antimicrobial and DPPPH scavenging activity. (5)
• Rhodomyrtone / Natural Antibacterial Potential: Study isolated Rhodomyrtone [6,8-dihydroxy-2,2,4,4-tetramethyl-7-(3-methyl-1-oxobutyl)-9-(2-methylpropyl)-4,9-dihydro-1H-xanthene-1,3(2H)-di-one] from Rhodomyrtus tomentosa (Aiton) Hassk. displayed significant antibacterial activities against against Gram+ bacteria including Bacillus cereus, B. subtilis, Enterococcus faecalis, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), S. epidermis, Streptococcus gordonii, S. mutans, S. pneumoniae, S. pyogenes, and S. salivarius. Results showed strong bactericidal activity on gram+ bacteria, including major pathogens. (6)
• Antibacterial / Leaves: Study evaluated karamunting leaf extract and fractions for antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa infection by agar well diffusion method. Chloramphenicol was used as standard positive control. An ethyl acetate fraction showed highest antibacterial activity against both pathogens. (7)
• Antioxidant / Leaves: Study evaluated both invitro and invivo antioxidant activities of R. tomentosa leaf extract. In vitro, using lipid peroxidation inhibition capacity, FRAP, and metal chelating activity, the extract exhibited concentration dependent free radical scavenging effects. In vivo in Swiss albino mice, the extract at 0.8 g/kg prevented the CCl4-induced alterations in antioxidant enzymes (SOD, CAT, GPx,), TBARS, and GPx and maintained antioxidant status. Results suggest potent antioxidant activity. (8)
• Anti-Inflammatory / Leaves: Study evaluated the effects of methanol extract of leaves on the production of inflammatory mediators (nitric oxide[NO],prostaglandin E2 [PGE2]) and the molecular mechanism of mediated inhibition, including target enzymes, with RAW264.7, peritoneal macrophages, and HEK293 cells. The ME clearly inhibited the production of NO and PGE2 in LPS-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. The anti-inflammatory properties may be attributed to suppression of Syk/Src/NF-kB and IRAK1/IRAK4/AP--1 pathways, with potential for development of a herbal remedy for prevention and/or cure of various inflammatory diseases. (9)
• Antiulcer / Antioxidant / Leaves: Study evaluated the antioxidant and antiulcer potential of various Rt leaves extracts. In an ethanol induced acute gastric ulcer model, the aqueous alcoholic, ethyl acetate, and water extracts showed significant dose dependent decrease in ulcer index in rats comparable to standard drug Omeprazole (2 mg/kbw). Extracts also exhibited significant free radical scavenging activity in the invitro antioxidant models i.e., DPPH. ABTS, nitric oxide, and H202 scavenging assays. The antiulcer activity may be attributed to their antioxidant mechanism. (10)
• Effect on Virulence Factors of Candida albicans and Human Neutrophil Function / Leaves: Study evaluated the anti-virulence and immunostimulatory activity of R. tomentosa ethanolic leaf extract against C. albicans. The extract showed significant inhibition of mature biofilm after treatment. At 50 µg/mL, there was significantly enhanced phagocytosis and killing of neutrophils against the organism. Results showed the extract exhibited a dual mode of action, inhibiting virulence factors and enhancing neutrophil functions. (11)
• Nanoherbal Haramonting / Potential and Toxicity: Nano-sized drugs have high loading capacities and can be given at high concentrations. Study evaluated the effect of nanoherbal haramonting on the histology of the liver, kidneys, lungs, heart, and brain. The nanoherbal harmonting contained flavonoids, steroids, glycosides, saponins, and tannins. LC50 and LD50 values were 2961.535 ppm and 10.4 mg/kbw, respectively. (Low LD50 valuse are associated with high toxicity.) Histology of the heart, kidney, lungs, and brain were changed and affected by haramonting treatment at each dose level. Study suggests nanoherbal haramonting has strong antioxidative activity and small size, and can be effectively used as medicine in the future due to its secondary metabolite contents. However, it has mild toxicity. (12)
• Antidiabetic / Cytotoxic / Antioxidant / Leaves: Study evaluated the antidiabetic, antioxidant, and cytotoxxic properties of R. tomentosa leaf extracts. A methanolic extract yielded highest values for total phenolic (191.97 mg GAE g) and flavonoid (29.11 mg QE g), AMD highest DPPH and ABTS activities with IC50s of 7.79 and 4.03 µg/mL, respectively, and highest FRAP activity wit 64.05 µM Fe2+ g. The ME showed cytotoxicity against MCF-7,HeLa, A549, and B16 cancer cell lines with IC50s of 123.49, 28.28, 168.88, 42.44 µg/mL, respectively. In invitro antidiabetic evaluation, the ME inhibited α-amylase and α-glucosidase with IC50s of 41.31 and 45.73 µg/mL, respectively. Results suggest a potential source of antioxidant, cytotoxic, and antidiabetic agents. (14)
• Anti-Staphylococcal Food Preservative / Leaves: Study evaluated the potential use of R. tomentosa leaf extract (RTEL) as an alternative food preservative agent for controlling the growth of Staphylococcus aureus. Salad dressing was used as a food model to study bactericidal properties and consumer acceptability. Results indicated RTEL is safe and effective as a natural anti-staphylococcal controlling agent that can be utilized in food systems. Further study is required on the effects of enterotoxin production, an important virulence factor of S. aureus responsible for food-borne disease. (15)
• Effect on Lipid Profile / Antioxidant / Fruits: Study evaluated the antioxidant activity of R. tomentosa fruit extract and its effect on triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDLO) and lipid peroxidation in induced-cholesterol New Zealand White Rabbits. At 200 µg/mL, a methanol extract showed 62.13% inhibition of DPPH free radicals with IC50 of 107 µg/mL, and at 500 µg/mL showed highest absorbance (0.16) for antioxidant activity in FRAP assay. The group treated with 50 mg/kg fruit extract showed significantly reduced TC, TG, LDL, and significantly increased HDL (p<0.05), along with significantly reduced lipid peroxidation indicated by low TBARs-MDA level. Results showed hypocholesterolemic effect and increased HDL, which can prevent formation of atherosclerosis in NZ white rabbits. (16)
• Safety Assessment of Rhodomyrtone / Leaves: Rhodomyrtone, a bioactive acylphloroglucinol compound from the leaves of R. tomentosa has been shown to be a potent antibacterial agent. Study evaluated the safety of rhodomyrtone in both invertebrate and vertebrate models. Rhdomyrtone did not cause signs of toxicity in invertebrate (Galleria mellonella) and vertebrate (zebrafish, murine) models. At 256 µg/mL, it did not cause observable human erythrocyte hemolysis. At MIC of 0.5-1 µg/ml against most gram+ pathogens, results suggest it should not cause toxic effects at concentrations used in humans. (17)
• Effect on Diabetic Wound Healing / Leave Ointment Formulation: Study evaluated the effect of ethanol extract ointment of karamunting leaves on the topical healing of diabetic wounds in rats. Application of the ointment affected the number of inflammatory cells, fibroblasts, and collagen density, as well as significant re-epithelization speed compared to diabetes controls. Of the three ointment formulations, 2.5%, 5%, and 10%, the 10% concentration showed comparable results to honey. Results suggest ethanol extract ointment of 70% karamunting leaves can increased the speed of diabetic wound healing. (18)
• Effect on Killing Activity of Human Neutrophils against Enterohemorrhagic E. coli / Leaves: Enterohemorrhagic Escherichia coli O157:H7 is one of the most virulent causative agents of foodborne disease. Use of antibiotic against E. coli O157:H7 infection leads to hemolytic uremic syndrome. Study evaluated the potential of ethanolic leaf extract of R. tomentosa in enhancing the killing activity oh human neutrophils against E. coli O157:H7. Results suggested the extract exhibited dual effects as immunostimulant and membrane permeabilizing agent perhaps resulting in enhanced killing activity of neutrophils against the organisms. (19)
• Rhodomyrtus / Wound Healing Potential: Study evaluated a crude ethanolic extract of R. tomentosa for phytohemical composition and presence of rhodomyrtone and SERT's in vitro wound healing activity. Phytochemical study yielded saponins, flavonoids, tannins, and steroid. LC-MS analysis showed presence of rhodomyrtone. SERT exhibited proliferative and migratory rate in human fibroblast cells (CRL 2522) in a dose-dependent manner, which supports the wound healing process. Bioactive compounds exhibited wound healing activities at 0.325 up to 2.5 µg/mL. (20)
• Rhodomyrtone / Effect on Biofilm-Forming Staphylococci: Study evaluated the anti-staphylococcal activity of ethanol extract of R. tomentosa and its pure compound, rhodomyrtone, and their effects on staphylococcal biofilm formation and biofilm-grown cells. Results showed ability to reduce biofilm formation and kill mature biofilms in a dose-dependent manner. Results suggest potential for further drug development for treatment of biofilm-forming staphylococcal infections. (21)
• Rhodomyrtone in Acne Vulgaris / Clinical Trial: Randomized and double-blind controlled clinical trial of 60 volunteers with mild to moderate acne evaluated rhodomyrtone as a potential natural alternative for the treatment of acne vulgaris. A 1% liposomal encapsulated rhodomyrtone serum was compared with a marketed clindamycin gel. Volunteers applied samples to the acne lesions on their faces twice daily. At the end of the clinical trial, total inflamed acne counts were significantly reduced by 36/36% compared to 34.70% in the clindamycin-treated group (p<0.05). Results suggest rhodomyrtone to be effective and safe for the treatment of inflammatory acne lesions. (22)
• Anti-Acne / Leaves: Propionibacterium acnes is recognized as one of the main causative agents in the pathogenesis of acne. Twenty-one isolated of P acnes isolated from acne lesions were screened for lipase and protease activity which are associated in acne and inflammation. All the isolates demonstrated lipase activity. Similarly, 90% produced protease enzyme. Leaves and rhodomyrtone were tested against P. acnes using broth macrodilution method. MIC90 for the ethanol extract of leaves and rhodomyrtone were 32 and 0.5 µg/mL, respectively. Number of bacterial cells were reduced by at least 99%. Cytotoxicity test of the extract and rhodomyrtone showed IC50s of 476 and >200 µg/mL, suggesting very low toxicity of both substances, which could be applied as topical therapeutic anti-acne agents. (23)
• Tomentosenol A / Antimicrobial / Cytotoxic / Leaves: Study of leaves isolated tomentosenol A (1), along with a pair of epimers, 4S-focifolidione (2) and 4R-focifolidione (3). Compound 1 showed excellent antimicrobial and cytotoxic activities. (24)
• Decreased Microbial Adhesion to Plastic Surface and Human Buccal Epithelial Cells / Leaves: Study evaluated the effect of R. tomentosa leaf extract and rhodomyrtone on adhesion of some oral pathogens to polystyrene plastic surface and human buccal epithelial cells. All pathogenic microorganisms treated with the extract and rhodomyrtone at their subinhibitory concentrations resulted in a decrease in their adherence ability to both plastic surface and buccal cells. Results showed the leaf extract and rhodomyrtone inhibit oral microbial adhesion. The anti-adherence activity can be useful in treatment or prophylaxis of oral infections. (25)
• Antimicrobial Electrospun Nanofibers: Electrospun nanofibers were prepared from R. tomentosa extract and poly(vinyl alcohol) and assessed for antimicrobial effect against two Gram- bacteria (E. coli , P. aeruginosa) and two Gram+ strains (B. subtilis, E. faecalis). An ethyl acetate extract was selected for fabrication of the nanofibers because it exhibited most active antimicrobial activity. The abundance of myricetin and rhodomyrtone might contribute to the antibiotic activity against tested bacterial strains. Antimicrobial activity of the nanofibers was higher at extract concentration of 1.5% and 2.5% against all test organisms with clear zone of inhibition of 7-12 mm. Results suggest an interesting platform for delivery of bioactive compounds for wound dressing or other strategies for treatment of bacterial infections. (26)
• Alternative Food Additive for Control of B. cereus / Leaves: Bacillus cereus is a Gram+, aerobic to facultative anaerobic, endospore-forming, rod-shaped bacterium, one of the most common foodborne pathogens, causing both intoxications and infections. Study evaluated the antibacterial properties of ethanolic extract from R. tomentosa leaves against Bacillus cereus by disc diffusion method against 65 food isolates. Antimicrobial activity on vegetative cell and endospores of a representative B. cereus isolate (MIC 32 µg/ml was assessed by enumerating viable cells at various time intervals. Application of extract in precooked rice and tuna steak showed decreased number of viable cells and endospores in both models after exposure to 16 and 32 MICs. Results suggest an alternative food additive for controlling B. cereus without compromising food safety. (27)
• Biologic Activity of Fruits / Antioxidant / Anti-Inflammatory: Study evaluated toe potential bioactivities of 80% ethanol extract of Sim fruits (EESF) in scavenging free radicals, suppressing pro-inflammatory mediator production, and inhibiting histamine release in vitro. The EESF scavenged DPPH and ABTS radicals with IC50s of 94 and 83 µg/ml, respectively. NO production and iNOS expression were suppressed at a dose-dependent manner in lipopolysaccharide-stimulated RAW 264.7 cells. The extract also reduced histamine release from calcium ionophore-activated RBL-2H3 mast cells. Results suggest a promising biomaterial for alternative medicine. (28)
• Biologic Activity of Fruits / Antioxidant / Anti-Inflammatory: Study evaluated the inhibitory effect of fruit extract of allergic responses in calcium ionophore A23187-activated RBLp2H3 mast cells. The fruit extract inhibited mast cell degranulation via decreasing ß-hexosaminidase release and intracellular Ca2+ elevation at concentration of 400 µg/mL. There was also a suppressive effect on production of
IL-1ß and TNF-α, effective scavenging of DPPH radical and suppression of RAS generation in a dose dependent manner. Results suggest a promising inhibitor or allergic responses and a potential as bioactive ingredient in the prevention of allergic diseases. (29)
• Effect on Proteins TGFß1 and VEGFR Proteins in Progression of Cervical Cancer: The process of angiogenesis in cervical cancer depends on VEGFR activity. Increased TGFß1 production is linked to cervical cancer, suggesting gene activation contributes to the emergence of cervical carcinoma. The elevated expression of TGFß1 and VEGFR in cervical carcinoma cells with poor histological characteristics are important in the neoangiogenesis and progression of cervical cancer. In a study on rats, R. tomentosa has been shown to heal carcinogenic metastatic carcinoma tissue, administered at various doses to decrease the number of brown nuclei that exhibit a positive index of TGFß1 and VEGFR expression in cancer tissues. Administration of R. tomentosa can repair tissue damage and decrease expression of TGFß1 and VEGFR via histological parameters. (30)
• Potential Bio-Control against Listeria monocytogenes: Listeria monocytogenes is an important foodborne pathogen implicated in many outbreaks of listeriosis. Study evaluated the potential use of R. tomentosa ethanolic leaf extract as bio-control agent against L. monocytogenes. Twenty-two L. monocytogenes isolates were checked with 16 commercial antibiotics and isolates displayed resistance to 10 antibiotics. All tested isolates were sensitive to the extract with inhibition zones ranging from 14-16 mm. MIKC and MBC ranged from 16 to 32 µg/mL and 128 to 512 µg/mL, respectively. Electron microscopy revealed fragmentary bacteria with changes in the physical and morphological characteristics. Results suggest potential for the extract as a bio-control agent to prevent Listeria moncytogenes contamination. (31)
• Potential as Antiseptic on Wound Healing / Leaves: Study evaluated the effectiveness of antiseptic solution of R. tomentosa (15%, 30%, and 60%) leaf extract on wound healing in male Wistar rats. Results showed significant difference in reduction in wound length between five experimental groups. The leaf extract accelerated the increase in the number of fibroblasts; however, there was no difference in wound healing length. (32)
• Inhibition of MRSA Adhesion, Invasion and Intracellular Survival in HaCaT Keratinocytes / Leaves: Methicillin-resistant Staphylococcis aureus (MRSA) has the ability to invade nonprofessional phagocytic cells, resulting in persistent infections and most likely host cell death. Study evaluated the potency of R. tomentosa leaf extract in intracellular killing of human HaCaT keratinocytes. Pretreatment of MRSA with extract resulted in a remarkable reduction in bacterial adhesion to HaCaT keratinocytes, with at least 60% inhibition of bacterial invasion into HaCaT cells. Intracellular killing shown by the extract demonstrated strong antibacterial activity against intracellular MRSA at non-toxic concentrations. Fluorescence microscopy showed the extract decreased MRSA-induced apoptosis in HaCaT ce3lls. There was also at least 50% reduction of cytotoxicity of HaCaT cells caused by MRSA supernatant. Results suggest potential for the extract as alternative treatment of MRSA infections in slight acidic compartments, particularly skin infections (33)
• Effect of Age and Maturity Level on Leaves and Fruits: Study evaluated the distribution of flavonoid and antioxidant activity based on age of leaves and maturity of fruit. The extract of young leaves showed stronger antioxidant activity than old leaves ( IC50s of 14.67 and 19.86 ppm, respectively). Antioxidant activity of purple fruits was stronger then red and green fruits (IC50s of 12.98, 28.63, and 48.36 ppm, respectively). The information may be useful in development of karamunting as potential source of natural antioxidants for functional foods and health products. (34)
• Antimicrobial Acylphloroglucinols / Leaves: Studyof leaves isolated 14 compounds including a new acylphloroglucinol, named tomentosone (1), and a new flavonol glycoside, myricetin-3,7,3'-trimethyl ether-5'-O-ß-glucopyranosdie (2). Study of n-hexane and EtOAc-soluble fraction of ethanol extract of leaves showed compound 1 and the known acylphlorogluciinol rhodomyrtone (3) exhibited significant antimicrobial activity with MIC of 3.66 and 1.83 µg/ml, respectively, toward Staphylococcus aureus. (35)
• Effect on E. coli-Induced Puerperal Infection / Leaves: Puerperium infection contributed 11% of 48.17% maternal mortality during the puerperium period, and one of the causes of increased risk of puerperium infection was Gram(-) Escherichia coli. Study evaluated the effect of R. tomentosa leaves ethanol extract (Rtl-EE) as an antibacterial on the spleen, liver, and uterus of E. coli-induced puerperal infection model in mice. Results showed administration of Rtl-EE decreased the growth of bacterial colonies in the liver, uterus, and spleen. Leaves contain active compounds i.e., phenols, flavonoids, saponins, tannins, alkaloids, and triterpenoids as antibacterial. (36)
• Myricetin / Attenuation of Inflammatory Response / Fruits: Histamine plays a key role in inflammatory responses via increasing chemokine adhesion molecule production and augmenting vascular permeability in endothelial cells. Study evaluated the role of phenolic compound, myricetin, in the down-regulation of histamine induced EA.hy926 endothelial cell activation. Myricetin was effective in suppression of IL-8 and MCP-1 productions and adhesion molecule generation. NF-kB activation was inhibited via reduction of IkB-α phosphorylation and p50/p65 subunit level. Myricetin potentially attenuated vascular permeability of endothelial cells through a decrease in eNOS phosphorylation and intracelluar calcium elevation. Results suggest promising pharmaceutical property for the amelioration of endothelial inflammatory responses. (37)
• Molecular Docking Study / Alkaloid Derivative Compound Against α-Glucosidase Enzymes / Antidiabetic / Stem: Study evaluated the binding score of alkaloids-derived compounds (homolycorine, ismine, lycorine, maritidine, tazetine) with protein α-glucosidase and the proteins's active site bound to the ligand. Results showed the average score for anchoring alkaloid-derived compounds with protein
α-glucosidase is 83.84%, a number which indicates that karamunting stems can be used as antidiabetic. (38)
• Hypocholesterolemic / Antiatherosclerotic / Fruit Juice: Study evaluated the pharmacologic properties of R. tomentosa fruit juice in Sprague-Dawley rats fed with a high fat high cholesterol die (HFHC) as antihypercholesterolemic and antiatherosclerotic agents. Results showed supplementation significantly prevented increases in total triglycerides, total cholesterol, LDL, and increased HDL lipoprotein in the serum. Supplementation prevented thickening of blood vessel wall, deposition of lipid formation and foam cells in the tunica intima of the aorta and coronary arteries. Study suggest supplementation with Rt fruit juice prevents hypercholesterolemia and atherosclerosis. (39)
• Hypocholesterolemic / Antiatherosclerotic / Fruit Juice: Study evaluated the anti-inflammatory activity of Rt leaves by in vitro red blood cell membrane stabilization methods. Inhibition of red blood cells membrane lysis showed the n-hexane fraction (25 ppm), ethyl acetate fraction (50 ppm), was water fraction (50 ppm) showed inhibition levels of 54.5, 81.8, and 63.6%, respectively. Oleanonic acid and ursonic acid were similar metabolites found in the EA subfractions 1, 2, and 3, which may have anti-inflammatory properties. The anti-inflammatory potency of the leaves was attributed to increase of red blood cell membrane stability equal to lysosome cells, depending on concentration (40)
• Anti-Metastatic on Human Skin Cancer Cells / Rhodomyrtone / Leaves: Study evaluated the inhibitory effect of rhodomyrtone isolated from the leaves of Rt on cancer metastasis in epidermoid carcinoma A431 cells and its underlying molecular mechanism. Rhodomyrtone at subcytotoxic concentration (0.5 and 1.5 µg/ml) exhibited pronounced inhibition of cancer metastasis by reducing cell migration, cell adhesive ability, and cell invasion of A431 cells in a dose dependent manner. Rhodomyrtone inhibited A431 cell metastasis by reducing MMP-2/9 activities and expression through inhibition of ERK1/2, p38, and FAK/Akt signaling pathways via NF-kB activities. Results suggest potential as a novel antimetastasis agent for the treatment of skin cancer cells. (41)
• Antidiarrheal / Leaves: Study evaluated the combination of n-hexane and ethyl acetate fractions from Rt leaves as antibacterial in an invivo method using white male rat Wistar strain induced by Shigella dysenteriae. The combination of fractions at dose of 100 mg/kbw reduced the population of Shigella dysenteriae to zero after 12 days of treatment. The fractions contained alkaloids, steroids, phenolics, and flavonoids. The reduction in bacterial colonies were similar to ciprofloxacin. Study suggests potential in dysentery medicine. (42)
• Tomentodione E / Meroterpenoids / Antiviral / Leaves: Study of leaves isolated a new meroterpenoid, tomentodione E (1), along with four known ones (2-5). Compound 1-4 were evaluated for invitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay. Compound 2 showed potent in vitro anti-RSV effect. (43)
• Antibacterial Essential Oil / Leaves: Study evaluated the antibacterial activity of essential oils from rose myrtle leaves against Shigella dysenteriae and Salmonella typhi. Agar diffusion method was used to test the antibacterial activity of EO. The n-hexane and ethyl acetate extracts were active against both bacteria. Isolates N1 and E1 produced from the extracts showed MICs of 125 µg/mL for both S. typhi and S. dysenteriae. Isolate N1 EO contained menthol (59.60%), caryophyllene (25.77%), and cubenol (14.63%) while E1 EO contained menthol (73.93%), pentanone (8.30%), alpha calacorene (7.58%), and calacorene (3.78%). Results suggest the leaves as a potential source of drug to treat dysentery and typhoid fever. (44)
• Piceatannol / Phenolic Profile of Fruits: Study evaluated the phenolic profile of sim fruit and the effect and changes in content during maturation, and variations induced by environmental conditions. HPLC-ESI-HR-MS studies revealed 19 phenolic compounds (PCs), which included stilbenes and elagitannins as major components, followed by anthocyanins, flavonols, and gallic acid. The PCs further quantified by HPLC-DAD, yielded piceatannon, as the major OC in the fruit, with a concentration of 2.3 mg/g dry weight at full maturity stage. It is a concentration 1000-2000 times higher than red grapes, a major source of stilbene in the human diet. During maturation, piceatannol and other stilbenes, ellagitanins, and flavonols decreased while anthocyanin content increased. Shade-grown sim trees showed significantly higher piceatannol than sun-exposed fruits. Results suggest an underutilized species, a potential source of health-promoting fruits. (45)
• Antibacterial / Anti-Streptococcus pneumonia Biofilm / Leaves: Study evaluated the effects pf Rt ethanol leaf extract and its potent purified compound, rhodomyrtone, on Streptococcus pneumoniae virulence factors including biofilms, capsule formation, and invasiveness. The extract of rhodomyrtone exhibited excellent antibacterial activity against S. pneumoniae with MIC ranging from 16-32 µg/ml and 0.125-1 µg/ml, respectively. At i/8xMIC, the extract of rhodomyrtone significantly inhibited biofilm formation in all clinical isolates (p<0.05), with 40-90% reduction in bacterial adhesion and invasion to A549 human alveolar epithelial cells. There was 90-99% increase in phagocytosis of bacterial cell by RAW264.7 macrophage cell line. Results suggest potential benefits for treatment of pneumococcal infections. (46)
• Effect on Skin Microbiota / Acne / Fruit: Study evaluated the skin microbiota with a focus on Cutibacterium acnes phylotypes i subjects with acne and determined microbiota changes after 28 days of treatment with berries of R. tomentosa as active ingredient. Reduction of retentional and inflammatory lesions were noted only after R. tomentosa treatment. Results suggest Rt extract acts as a microbiota-regulating agent. (47)
• Injectable Hydrogel Formulation as Potential Wound Dressing Material: Study reports on a simple and effective method of fabrication of a multifunctional alginate hydrogel (Alg@Rt) with anti-inflammatory and antibacterial activities, by combining the advantages of alginate and R. tomentosa leaves extract. The new injectable Alg@Rt hydrogel was developed to facilitate wound healing process. Compared to pure Alg hydrogel,, the Alg@Rt hydrogel significantly enhanced the anti-inflammatory, antibacterial, and cell proliferative activities, beneficial in wound treatment and tissue regenerative applications. (48)
• Haramonting / Anticancer Molecular Strategy in Breast Histology: Study assessed the impact of haramonting on breast cancer by examining the expression of various biomarker proteins associated with breast cancer. Haramonting possesses the capacity to restore the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) to normal levels in the blood serum of rats afflicted with cancer. The histopathological analysis of the breast tissue revealed elevated levels of Her2, IL33, EGFR, and MUC1. There was a notable increase in the growth of epithelial cells, with two or more layers of cells reaching towards the center of the duct. Study suggests Haramonting may be effective in treating breast cancer. (49)
• Antitumor Triterpenoids / Roots: Study of roots isolated two new triterpenoids, tomentoids A and B (1,2), along with five known ones. Compounds 1 and 3-7 exhibited potent inhibitory effects on three tumor cell lines: BGC823, SGC7901, and SK-MEL-110. (50)
• Protection Against Allethrin-Exposed Pulmonary Damage: Inhaling Allethrin (C19H2603 may induce oxidative stress in lung cells by causing formation of free radicals. Interleukins (ILs) are cytokines or proteins and signaling molecules initially produces as immune response by leukocytes. Antioxidants from Rt may prevent lung damage induced by allethrin-containing electric mosquito repellents. Study evaluated rats exposed to allethrin via an electric mosquito repellent. Concentrations of pro-inflammatory cytokines IL-1ß, IL-8, IL-9 and IL-18 are elevated in both bloodstream and tissues after being exposed to electric mosquito repellent that contains allethrin. R. tomentosa has the potential to enhance alveolar histologic changes. Similar to Vitamin C, it reduces expression of IL-1ß, IL-8, IL-9 and IL-18, while increasing IL-6 and IL-10. (51)
• Nano Herbal Combination / Diabetic Wound Healing: Diabetic wounds can cause damage to skin tissue for a long time. Increased glucose levels affect angiogenesis which triggers the wound to heal. Study evaluated the IL-1ß expression in diabetic wound healing after being given a nano herbal of Zanthoxylum acanthopodium and Rhodomyrtus tomentosa. Results showed significant difference in IL-1ß expression. Histologically in wound healing, granulation tissue of blood vessels is dominated by extensive fibroblasts and collagen. Epithelium covered the wound that occurred on the skin, suggesting some compounds in the nano herbal haramonting and andaliman can stimulate cell division and growth to form scar tissue. Results suggest the nano herbal formulation of Rt and Za can be developed to treat wounds in diabetics. (52)
• Protection from Exposure to Electric Cigarette / Leaves: Cigarette smoke contains free radicals. Antioxidants in harmonting can neutralize free radicals. Study evaluated the effect of harmonting leaf extract as antioxidant to histological pancreas of mice exposed to electric cigarette. (53)
• Anthracene Glucosides / Stimulation of Osteoblastic Differentiation / Aerial Parts: Study of aerial parts isolated two new anthracene glycosides, 4,8,9,10-tetrahydroxy-2,3,7-trimethoxyanthracene-6-O-β-D-glucopyranoside (1) and 2,4,7,8,9,10-hexahydroxy-3-methoxyanthracene-6-O-α-L-rhamnopyranoside (2), along with three known compounds (3-5). Compounds 1, 2, and 5 significantly (p<0.05) increased alkaline phosphatase activity, collagen synthesis, and mineralization of the nodules of MC3T3-E1 osteoblastic cells. (54)
• Mitigation of Intestinal Barrier Dysfunction / Fruit: Study evaluated the mitigative effect of phenolic-rich Rt fruit extract on high fat diet (HFD)-induced intestinal barrier dysfunction in mice and the underlying mechanism. Results showed extract supplementation improved gut microbiota dysbiosis induced by HFD. Extract intervention mitigated intestinal barrier dysfunction and inflammation by elevating tight junction proteins expression levels and decreasing proinflammatory cytokine levels. Extract supplementation also inhibited HFD-induced trigger of the lipopolysaccharide-toll-like receptor 4-nuclear factor kappa B (LPS-TLR4-NFkB) pathway in colonic tissue. Extract supplementation may be an effective way to protect the intestinal tract in HFD-induced obese individuals. (55)
• Watsonianone A / Attenuation of RSV-Induced Inflammation / Fruit: Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Study isolated watsonianone A (WA) from the fruit of R. tomentosa, which was found to show good inhibitory effect on RSV-induced NO production, with half-MIC of 37.2 µM. Immunosorbent assay and PCR analysis indicated the watsonianone A markedly reduced both mRNA and protein levels of TNF-α, IL-6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, WA inhibited NF-kB activation by suppressing IkBα phosphorylation. WA also activated the thioredoxin system and decreased intracellular ROS levels. Results suggest watsonianone A can attenuate RSV-induced inflammation via suppression of ROS-sensitive inflammatory signaling. (56)
• Cytotoxicity / Antioxidant / Leaves: Study evaluated an ethanol extract of R. tomentosa for antioxidant properties and cytotoxicity against RAW264.7 macrophage cells. The EtRT showed dose dependent ability to scavenge DPPH radicals and reduce ferric ions in FRAP. The EtRT did not show cytotoxicity to RAW264.7 macrophage cells at concentrations of 3.91 µg/mL. EtRT showed ability to inhibit ROS production on LPS-induced RAW264.7 macrophage cells at 7 µg/mL. Results suggest the EtRT extracts have potential to reduce LPS-induced oxidative stress due to antioxidant activities of phenolic compounds in the extract, and has potential as a natural agent for treatment of oxidative stress. (57)
• Antibiofilm Producing / Antiquorum Sensing: Biofilm formation is a potentially important mechanism that contributes to antibiotic failure on Streptococcus pyogenes. Study evaluated the effect of three plants viz., Boesenbergia pandurata, Eleutherine americana, and Rhodomyrtus tomentosa. R. tomentosa extract significantly prevented biofilm formation (0.24-7.81 µg mL-1) A correlation between antiquorum-sensing and antibiofilm producing activities was demonstrated. Strong inhibition of quorum sensing was displayed by Rt extract. (58)
• Acetylcholinesterase Inhibitory / Polymethylated Acylphloroglucinol / Twigs and Leaves: Study of twigs and leaves isolated a novel polymethylated phloroglucinol meroterpenoid (PPM), rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs), rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two ß-triketone units, rhotomentosone F (7), and five known analogues (8-12). Compound 6 exhibited significant AChE inhibitory effect with IC50 of 8.68 µM, which also interacted with AChE residues Ser125, Glu202, and Tyr133 crucial for AChE inhibitory activity. Study provides potential lead compounds for development of new AChE inhibitors for treatment of Alzheimer's disease. (59)
• Antithrombotic Effect / Potential Natural Anticoagulant / Leaves: Study evaluated the antioxidant and anticoagulant properties of Rt leaves ethanol extract in vitro. RtEE 1 mg/mL showed phenolic content (TPC) of 10.82 mg GAE/g, flavonoid content (TFC)of 2.40 QE/g. APTT, PT, and TT were significantly (p<0.001) prolonged in both Rt-EE and piceatannol (PIC), with concentrations ranging from 15.62 up to 1000 mg/mL. Results showed both PIC and RtEE showed antithrombotic properties, the latter attributed to total phenolic and total flavonoid content. (60)
• Histological Analysis of TGFß1 and VEGFR Expression in Cervical Carcinoma / Leaves: Cervical carcinoma is one of the most common malignant carcinomas in the world. The process of neoangio- genesis in cervical cancer depends on VEGFR activity. Increased TGFß1 production is also linked to cervical cancer, suggesting contribution of gene inactivation to the emergence of cervical carcinoma. Increased MDA and decreased SOD levels were observed in rats with cervical cancer. Administration of R. tomentosa leaf extract balanced SOD and MDA levels. Higher doses of Rt were associated with higher SOD and lower MDA levels. Elevated expression of TGFß1 and VEGFR in cervical cancer cells with poor histological characteristics show how important these proteins' actions are in neoangio-genesis and progression of cervical cancer. TGFß1 expression was shown to decrease as the dose of R. tomentosa was increased. R. tomentosa has been shown to heal carcinogenic metastatic carcinoma tissue, and in various doses was shown to decrease the number of brown nuclei that exhibit a positive index of TGFß1 and VEGFR expression in cancer tissues. (61)
• Effect of Nano Herbal Haramonting on Testis Histology / Leaves: Study evaluated the testis histology of male mice (Mus musculus) after giving nano-Rhodomyrtus tomentosa. Leaves of haramonting were made into nanoherbal using high-energy milling and treating mice for 14 days. While there was not significant difference in weight (p>0.05), there was significant difference in spermatogonia, spermatocytes and spermatid. Results suggest excessive doses of nano-Rt can cause damage to testicular cells and interfere with the process of spermatogenesis, and cause infertility. (62)
• Comparative Antioxidant and Digestive Enzyme Inhibitory Activities / Fruits in Two Ripening Stages: Study evaluated the antioxidant properties and digestive enzymes inhibitory activities of unfully mature (UM-RTF) ad fully mature RTF (FM-RTF). FM-RTF showed high levels of energy, ascorbic acid, organic acids and total phenolics, with higher total phenolic content (TPC), but significantly lower total flavonoid content (TFC). FM-RTF exhibited higher antioxidant activities and digestive enzymes inhibitory activities than UM-RTF. The interaction between the main phenolic compounds and
α-glucosidase/α-amyase was preliminarily explored by molecular docking analysis. (63)
• Antidiabetic / Leaves: Study evaluated the antidiabetic effect of aqueous fraction of R. tomentosa leaves on male white mice induced with alloxan. Results showed doses of 10, 20, and 40 mg/kbw decreased blood glucose levels of alloxan-induced diabetic mice (p<0.05). (64)
• Hepatoprotective Against Antitubercular Drugs / Leaves: Study evaluated the hepatoprotective activity of aqueous alcoholic extract (70%) extract of leaves of Rt against antitubercular drug-induced hepatotoxicity and its antibacterial activity against Gm(+) and Gm(-) microorganisms. Extract showed an LD50 up to 2000 mg/kg with no mortality suggesting nontoxic nature and safety. Toxicants induced elevations of SGPT, SGOT, total bilirubin, ALP, and TBARS, which were significantly reduced by the extract at 200 and 400 mg/kbw. Histopathological changes, steatosis, necrosis, etc. were partly or completely prevented in animals treated with the extract. Extract also showed good antibacterial activity against all Gm(+) bacteria and E.coli. The RT extract also showed good antimycobacterium activity with MIC at 12.5 µg/ml. (see constituents above) (65)
• Triterpenoid Rhodotomoside A / α-Glucosidase Inhibitory / Leaves: Study of leaves isolated a new triterpenoid, 2α, 3β, 23α, 29-tetrahydroxyolean-11, 13 (18)-dien-28, 19β-olide, rhodotomoside A (1), along with 6 known triterpenoids (2-7). Compound 1 showed inhibition rates of 77.82% to α-glucosidase with IC50 of 0.213 mg/mL. (66)
• Haemostatic Activity / Leaves: Study evaluated the potential of R. tomentosa as a native anticoagulant by evaluating possible haemostatic effect of aqueous leaf extract in vitro. Results showed markedly prolonged spikes of thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Results showed potent anticoagulant effect significantly higher in the extrinsic pathway (PT). Anticoagulant activity was attributed to tannins and flavonoids. (67)
• Tomentosones / Antimalarial / Leaves: Study of CH2Cl2 extract of R. tomentosa leaves isolated two phloroglucinols, tomentosones A and B (1,2). Tomentosone A inhibited the growth of chloroquine-resistant and -sensitive strains of malaria parasite Plasmodium falciparum, with IC50s of 1.49 µM and 1.0 µM, respectively. Tomentosone B was significantly less active. (68)
• Nephroprotective Against Diabetic AGEs (Advanced Glycation End Products): Study evaluated the impact of karamunting on blood glucose profile, HbA1c, insulin profile, and kidney condition (AGEs [advanced glycation end products] expression, TNF-α, and kidney histology) in diabetic Wistar strain male rats. Results showed karamunting can improved blood glucose levels and HbA1c, prevent AGEs deposition in renal tissue, and prevent further damage and complications of kidney organs in diabetic rats. (69)
• Effect of Nanoherbal on Placental Histology of Preeclamptic Rats: Study evaluated the role of nanoherbal haramonting and extra virgin olive oil (EVOO) on placental preeclampsia (PE). Results showed significant differences in the systolic and diastolic blood pressures and proteinuria (p<0.05) and significant difference in the number of trophoblasts in the placenta of preeclampsia (p<0.05). Study suggests administration of EVOO and nanoherbal haramonting can improve trophoblast counts and placental histology. (70)
• Antityrosinase / Anti-Hyperpigmentaton / Antioxidant / Leaf, Flower, Fruit: Study evaluated the antioxidant and anti-tyrosinase activity of R. tomentosa leaf, flower, and fruit extracts. A methanolic extract of flower exhibited the highest radical scavenging activity (IC50 95 µg/ml), total phenolic content (100.467 mg GAE/g), and tyrosinase inhibitory activity (IC50 0.1 µg/ml). (71)
• Anti-Inflammatory in a Combination Model of Asthma and Coal Dust: Study showed a nebulizer extract of ethanol Karamunting leaves can significantly reduce the number of eosinophils, neutrophils, and lymphocytes in a combination model of asthma and coal dust. It can reduce lung tissue remodeling by decreasing the thickness of epithelial cells, smooth muscle cells, fibrosis of bronchioles subepithelial, and number of goblet cells in the same combination model. (72)
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