Malaysian Journal of Medicine and Health Sciences (eISSN 2636-9346) review ARTICLE

Malaysian sp: An Updated Review of Their Impacts on The Reproductive Functions and Fertility

Razif Dasiman1,3, Ebby Anuar Bahari2

1 Faculty of Health Science, Universiti Teknologi MARA, Selangor Branch, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia 2 Faculty of Medicine, Universiti Teknologi MARA, Selangor Branch, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia 3 Maternofetal and Embryo Research Group (MatE), Faculty of Medicine, Universiti Teknologi MARA, Selangor Branch, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia

ABSTRACT

Phyllanthus belong to the Phyllanthacea family, which consists of 60 other genera and about 2000 . Phyllan- thus contains numerous active compounds, such as alkaloids, flavonoids, coumarins, polyphenols, tannins, triter- penes, and sterols. Several studies have shown that Phyllanthus species have pharmacological effects. These include the properties of antioxidants, antimicrobials, anti-diabetic, anti-cancer, anti-hyperglycemic, antispasmodic, and anti-hepatotoxic. In Malaysia, there are about 20 species of Phyllantus . However, only nine species were scientifically proven to improve health, mainly reproductive functions, and fertility. This review aims to summarize the current literature regarding Malaysian Phyllanthus species and discuss how they impact reproductive functions and fertility. Keywords: : Malaysian Phyllanthus, Health impacts, Reproductive functions, Fertility

Corresponding Author: However, little scientific evidence currently supports Razif Dasiman the use of Phyllanthus on reproductive functions and Email: [email protected] fertility. Tel: +603 32584390 Humans are exposed to dozens of chemicals and pollutants, which can perturb homeostatic imbalances and alter normal biological functions. Exposure to INTRODUCTION environmental pollutants is suggested to be one of the causes of chronic diseases such as cardiovascular diseases Malaysia’s rainforest is one of the richest tropical (CVD), neurodegenerative diseases, autoimmune rainforests globally, with various species of flora disorders, musculoskeletal diseases, reproductive and fauna. Its green biodiversity has allowed many problems, and infertility (6). More interestingly, stress has species to grow. These include herbs, lichens, also been a significant cause of infertility by exhibiting flowers, fruits, shrubs, and many more. Among them testosterone suppression, reducing spermatogenesis and are numerous species of medicinal plants that possess libido, contributing to sexual dysfunction (7). Medication high medicinal value. One of the that possesses and surgery are both used in treating sexual dysfunction. excellent diversity of secondary metabolites is the Herbal therapies, however, are a plausible solution for genus Phyllanthus. A number of plants in the genus individuals who seek to increase their sex drive due to the Phyllanthus have long been used in herbal formulations. existence of reliable contemporary treatments. In many Traditionally, herbs are used to treat various health countries, alternative medicine utilizes various trees and conditions such as digestive problems, kidney stones, shrubs as reproductive stimulants to enhance couples’ liver diseases, viral infection, genitourinary infections, reproductive performance. These include Eurycoma hypertension, respiratory illnesses, and skin conditions longifolia, Terminalia catappa, Lepidium meyenii, (1,2). In recent years, several studies on the ability of Tribulus terrestris, Montanoa tomentosa, Allium sativum, different bioactive components in Phyllanthus have Alpinia galangal, Anacardium occidentale, Anacyclus been undertaken. Some of the potentials reported are pyrethrum, Butea frondosa, Caesalpinia benthamiana, antioxidant activity, anti-diabetic, anti-cancer, anti- Cannabis sativa, Chlorophylum borivilianum, Citrullus mutagenic, anti-viral, and anti-obesity properties (3–5). lanatus, Ginkgo biloba, Hibiscus sabdariffa, and Fadogia

Mal J Med Health Sci 17(SUPP3): 343-350, Jun 2021 343 Malaysian Journal of Medicine and Health Sciences (eISSN 2636-9346) agrestis (8). In recent years, studies reported that some b. Phyllanthus emblica of the active compounds obtained from the Phyllanthus Phyllanthus emblica is also known as Pokok Melaka contribute to improving reproductive functions and and can be found in China, Malaysia, India, and enhancing fertility in males and females (9). Therefore, Indonesia. It has been widely used in many local herbal this review focuses on Malaysian Phyllanthus species medicines due to its anti-inflammatory and antipyretic and their impacts on male and female reproductive effects. The fruit is used as a tonic beverage, infertility functions and fertility. treatment, and cancer (3,10). Gallic acid, D-fructose, C-fructose, myo-inositol, coumarins, ellagic acid, Botanical perspectives of Malaysian Phyllanthus and its gibberellin, kaempferol, astragalin, leucodelphinidin, common active compounds quercetin, isoquercitrin, rutin, and lipids are active compounds present in Phyllanthus emblica (10). Phyllanthus are a very diverse genus of flowering trees, shrubs, and spurge family herbs (Euphorbiaceae). The c. Phyllanthus niruri plants are deciduous and floriferous with flattened green Phyllanthus niruri is native to the Amazon rainforest, roots, which acts as leaves called phyllodes. Some including South East Asia, Southern India, China, and other species have leafy twigs, with white or reddish flowers tropical regions. It is known locally as Dukung Anak. It is cover the stalk (1). It has been shown that most herbs historically used as anti-hyperglycemic, antispasmodic, of the genus Phyllanthus contain different secondary anti-hepatotoxic, anti-viral, anti-bacterial, laxative, metabolite combinations. Phytochemicals synthesized diuretic, carminative, antimalaria, jaundice, hepatitis from all these plants include flavonoids, polyphenols, B, cough, pneumonia, diarrhea, vaginitis, tumors, and and lignans (10). kidney stones (2,16). Some of the active compounds There are approximately 20 species of Phyllanthus in present in Phyllanthus niruri are nirurine, securinine, Malaysia, namely Phyllanthus albidiscus, Phyllanthus phyllanthine, gallic acid, corillagine, ellagic acid, emblica, Phyllanthus niruri, Phyllanthus debilis quercetin, quercitrin, isoquercitrin, rutin, astragalin, Phyllanthus amarus, Phyllanthus chamaepeuce, nircetin, hypophyllanthin, niranthin, niretralin, Phyllanthus gracilipes, Phyllanthus columnaris, lintetalin, hydroxynirathin, isolintetralin, linnanthin, Phyllanthus elegans, Phyllanthus filicifolius, Phyllanthus nirphyllin, ricinoleic acid, catechin, epicatechin, gomphocarpus, Phyllanthus columnaris, Phyllanthus gallocatechin, epigallocatechin, gallate, lupeol, oxyphyllus, and Phyllanthus pachyphyllus (2,11). Only phyllantenol, phyllathenone, and phyllantheol (1,4). two of Phyllanthus’s described species, Phyllanthus filicifolius and Phyllanthus watsonia, are endemic to d. Phyllanthus reticulatus Malaysia (11). Of the twenty species described, the Phyllanthus reticulatus is present in Africa, Bangladesh, nine species are Phyllanthus amarus, Phyllanthus China, Southeast Asia, Thailand, India, and Northern niruri, Phyllanthus columnaris, Phyllanthus emblica, Australia. Locally, it’s known as Kayu Darah belut. Phyllanthus recticulatus, Phyllanthus debilis, Traditionally, Phyllanthus reticulatus has been used as Phyllanthus urinaria, Phyllanthus watsonii, and a diuretic to encourage fertility in women, treat piles Phyllanthus pulcher have been thoroughly investigated. and hemorrhoids, remedy hookworms, toothache, Researchers attempt to unravel the plants’ medicinal venereal sores, and smallpox syphilis, asthma, and sore properties, exposing their hidden potential, followed throat (17). 1-octacosanol, 1-teracosanol, 1-tricosanol, by claims of additional beneficial health effects. pyrogallic acid, gallic acid, ellagic acid, coumaric acid, tricin, pirorisinol, beta-sitosterol, daucosterol, a. Phyllanthus amarus stigmasterol, friedelin, 21-hydroxyfriedelin, friedelanol, Phyllanthus amarus has been found in the Bahamas, and epi-friedeol are some of the active compounds Brazil, China, Ghana, India, Malaysia, Nigeria, the present in Phyllanthus reticulatus (1,17). Philippines, Thailand, and West Africa. It’s locally referred to as Dukung Anak (12). Phyllanthus amarus e. Phyllanthus urinaria has been commonly used as an ethnomedicine in Phyllanthus urinaria can be found in subtropical and different countries such as India to treat jaundice, tropical regions such as China, India, Thailand, Trinidad malaria, prevalent diseases, in Nigeria for stomach and Tobago, and South America. The plant was used to pain treatment, and in Brazil to treat fever and treat liver damage, hepatitis, jaundice, kidney diseases, kidney problems (13,14). It is used to treat diabetes, enteritis, diarrhea, and dropsy in traditional oriental hypertension, diarrhea, and poisonous insect bite medicine. Experimentally, some of the active compounds antidote in Malaysia (2). Alkaloids, dihydrosecurinine, found in Phyllanthus urinaria are hexacosanoic acid, tetrahydrosecurinine, securinine, securinol, phyllanthine, phyllanthin, phyllanthidine, alkanols; triacontanol, allosecurin, norsecurinine, quercetin, quercetin, gallic acid, phyllurine, ellagic acid, methybrevifolin 4-hydrosecurinine, 4-methoxydihydrosecurinine, carboxylate, trimethyl ester dehydrochebulic acid, 4-methoxytetrahydrosecurinine, epibubbialine, and astragalin, quercetin, quercitrin, isoquercitrin, rutin, isobubbialine are some of the active compounds found kaempferol, lactone glycosides, phyllanturinolactone, in Phyllanthus amarus (15). and lignanolactone (1,18).

344 Mal J Med Health Sci 17(SUPP3): 343-350, Jun 2021 f. Phyllanthus watsonii pheromones, and drugs (8,24). A small shrub that grows to about 15 cm in height, Phyllanthus watsonii is usually found near fast- Positive impacts of Phyllanthus on reproductive flowing rivers. The species is native to Rompin Endau, functions and fertility Malaysia. It has been used to treat cancers, including A brief report of current research on Phyllanthus on cancers of the cervix, liver, lungs, macrophages, reproductive functions and fertility potential is described uterus, stomach, breast, and colon. β-Sitosterol- as follows. Ojezele et al. (25) reported that treatment with β-D-Glucoside, β-sitosterol, lupeol, friedelin, Phyllanthus amarus seed extract showed a substantial glochidone, and glochidonol are some of the active increase in serum and semen testosterone levels, compounds present in Phyllanthus watsonii (1,19). sperm parameters, and morphology in Plasmodium bergheii treated mice. In another study by Obianime g. Phyllanthus columnaris and Uche (26), the methanol extracts of Phyllanthus Phyllanthus columnaris is a deciduous tree commonly amarus caused a non - significant enhancement in found in low-lying inland forests in India (Andaman the levels of luteinizing hormone (LH) and follicle- Islands), Bangladesh, Myanmar, Thailand, and Malaysia. stimulating hormone (FSH), thereby increasing libido The plant is used for various ailments, including and male reproductive function. Moreover, Azubuike smallpox, syphilis, asthma, and diarrhea. Some of the et al. (27) reported that the Phyllanthus amarus extracts compounds that have been isolated from Phyllanthus could increase serum testosterone levels, epididymal columnaris are taraxerol, taraxerone, friedelin, lupanyl sperm concentration, and sperm motility. Phyllanthin, acetate, lupeol, stigmasterol, lupeol acetate (1,20,21) a significant lignan derived from Phyllanthus amarus, demonstrated strong apoptosis activation in cervical h. Phyllanthus debilis cancer cells (28). Phyllanthus debilis can be found in a waste spot area. It is In addition, Priya and Islam (3) stated that Phyllanthus distributed in Thailand, India, Sri Lanka, Indonesia, and emblica increases the number of sperm and produces an Malaysia. Traditionally, it is used to treat various diseases, aphrodisiac effect in males. At the same time, it preserves including diabetes, jaundice, sickle-cell anemia, normal and stable menstruation in females, improves diarrhea, wounds, inflammation, intestinal worms, the reproductive tissue and ovaries, strengthens the scabies, gall stones, and kidney stones. The compounds uterus, prevents white discharge, relieves vaginitis, and isolated from Phyllanthus debilis are hypophyllanthin, protects the reproductive system. Iamsaard et al. (29) furosin, geranin, rutin, β-sitosterol, and gallic acid (1,22). demonstrated that Phyllanthus emblica significantly improved testicular weight, increased levels of i. Phyllanthus pulcher testosterone hormone and sperm concentration, and Phyllanthus pulcher is an ornamental plant that has been mitigated testicular impairment in valproic acid-treated used for problems with the stomach. It is known as Naga rats. On another note, Phyllanthus emblica was found to Buana as well. Historically, it is a cure for eye infections, protect the genotoxicity caused by cyclophosphamide nasal ulcers, abscesses, pruritus, problems with fever and in mice germ cells by substantially increasing the kidneys, stomach pain, and hypertension. Terpenoids, percentage of defects of the sperm head (30). glochidone, glochidonol, and lupeol are some of the In a study performed by Pryuttma and Parimal (31), compounds isolated from Phyllanthus pulcher (1,23). they emphasized that Phyllanthus emblica extract treatment was found to mitigate endosulfan’s toxic The mechanism involved in reproductive functions and effects by improving testicular weight, protecting fertility seminiferous tubules, germinal epithelium, Sertoli cells, and spermatogenic cells from injury. The effects Some medicinal plants have been shown to have of Phyllanthus emblica on males were also studied by an aphrodisiac activity that can enhance desire for Arun et al. (32). Their study reveals that Phyllanthus sex, boost libido, improve sexual performance and emblica has significantly increased sperm concentration, reproductive functions, and increase sexual duration. testosterone levels, and StAR protein expression. Besides, Interestingly, the reason behind this is that the central Phyllanthus emblica altered the tyrosine-phosphorylated nervous system controls and regulates sexual desire. The protein in the testis, decreased corticosterone and MDA mechanism involves incorporating tactile, olfactory, levels, reduced head defects in sperm, and acrosome- and mental stimuli. In some cases, it provides immediate reacted sperm in rats. actions to consumers by improving sexual performance Data from Madhavi et al. (33) also revealed that a and libido. It may affect blood flow across the genital significant reduction in the number of sperm head region, for instance, and then increase the duration defects had been recorded in heavy metal-treated of sexual activity. Besides, other types of aphrodisiac animals, suggesting that Phyllanthus emblica contributes plants consist of psychopharmacological compounds to modulating heavy metal mutagenesis in mammalian that cross the blood-brain’s barriers and induce some animals. In another research (10), the estrogenic regions of sexual arousal. These include the compounds’ and gonadotropic activities of Phyllanthus emblica interference with neurotransmitters, hormones, fruits affecting females’ reproductive parameters

Mal J Med Health Sci 17(SUPP3): 343-350, Jun 2021 345 Malaysian Journal of Medicine and Health Sciences (eISSN 2636-9346) were reported. The petroleum ether showed the most sperm of animals treated with Phyllanthus amarus. potent estrogenic and follicle-stimulating hormone-like On another note, the aqueous extract of Phyllanthus activity, and Phyllanthus emblica chloroform fractions amarus was reported to have an abortifacient effect demonstrated strong luteinizing hormone-like [LH] and decreased the implantation time frame (41). In the activity. In addition, neither estrogenic nor gonadotropic Ataman and Ikediashi study (42), the rats treated with activities were seen in the ethyl acetate fractionated ethanolic extract of Phyllanthus amarus showed various extract. testicular degeneration degrees, with a significant According to Giribabu et al. (34), the treatment of reduction in total sperm count, sperm concentration, Phyllanthus niruri leaf aqueous extract to rats in the and survival, and unflattering spermatozoa in the lumen diabetic group could mitigate oxidative stress in the of seminiferous tubules. The results also showed the kidneys and testes, preventing reduced amounts of differentiation and production of germ cells were stopped endogenous antioxidant enzymes. In another Phyllanthus in the lumen. Ronnie (43) discovered that oral treatment niruri study, Jia et al. (4) showed that corilagin derived with Phyllanthus amarus aqueous extract lowered the from Phyllanthus niruri serves as a natural, promising fertility index, reduced testicular and prostate weight, therapeutic agent against the growth of ovarian cancer reduced sperm parameters, impeded spermatogenesis, cells by targeting the TGF-β/AKT/ERK/Smadad/Smad/ and have had an estrogen-like effect on male rats. Smad/TGF signaling pathways. Phyllanthus niruri is another Phyllanthus species that Young et al. (35) have shown that phyllanthusmins exhibits anti-fertility properties. According to Ezeonwu from Phyllanthus poilanei serve as an inhibitor of late (44), the treatment of Phyllanthus niruri’s aqueous crude autophagy and primary antitumor efficacy through the extract contributed to a significant reduction in seminal autophagic pathway against ovarian cancer. Other than fluid fructose level and sperm parameters. On another that, Ndeingang et al. (36) stated that by decreasing cystic note, Phyllanthus niruri extract was found to decrease follicles, luteinizing hormone (LH), and testosterone mature spermatozoa and cause harmful testes (16). levels, Phyllanthus muellerianus could alleviate Degenerative effects on sperms and a significant reduction reproductive functions, hormonal levels, and structural in testosterone, estrogen, and progesterone levels were changes in PCOS rats, increase estradiol, and restore also reported in males treated with Phyllanthus niruri the estrus cycle after 14 days of treatment. In another (45). Moreover, the extract of Phyllanthus niruri was scenario (5), the administration of Phyllanthus fraternus demonstrated to alter somatic gonadal development, aqueous extract increased lipid peroxidation levels. It modified the corpus luteum function on synthesis showed a protective action against cyclophosphamide- and secretion of estrogenic hormones, reduced the mediated antioxidant depletion as restoring male mice’s number of embryos, and cause morphophysiological histopathological architecture. dysfunctions, which leads to miscarriage (46). Paula et al. (47) suggested that fetal macrosomia, excessive The negative impacts on reproductive functions and ossification areas, impaired maternal kidney weight, fertility and morphology, and reduced offspring weight were Besides having a good effect on reproductive functions influenced during fetal development by treating and fertility, there are also studies on Phyllanthus, Phyllanthus niruri aqueous extract. which bring about adverse effects to the reproductive functions of both men and women. Research by Bakare Common active compounds in Phyllanthus et al. (37) highlighted that by increasing the intensity that affect reproductive functions and fertility of micronucleated polychromatic erythrocytes and Interestingly, this review found three common active sperm abnormalities, the aqueous extract of Phyllanthus compounds in Phyllanthus, namely rutin, quercetin, amarus possessed metabolites that are able to cause and β-sitosterol, that have been actively studied and systemic and damage to DNA in the mouse and rat. reported. However, there are other active compounds in The results of Ataman and Sakpa (38) have generally the species that are yet to be discovered or studied on, established the anti-fertility effects of Phyllanthus amarus such as phyllantine, phyllantidine, gallic acid, corrilagin, on ovarian morphology and functions, which involves ellagic acid, kaempferol, astragalin, isoquercitrin, no implantation, resorption, and litters. Other than phyllanthin, hypophyllanthin, niranthine, niretraline, that, the levels of estrogen, FSH, LH, and progesterone isolintetraline, phyllester, daucosterol, geranin, furosin, have significantly reduced, impaired folliculogenesis, lupeol, and lupeol acetate. increased follicles of the atretic ovary, and degenerative ovarian stroma. a. Rutin More interestingly, a subchronic course of Phyllanthus Rutin is a flavonol glycoside that is important to protect amarus administration in rats possessed anti-fertility capillaries, prevent arteriosclerosis and high blood activity and has shown a substantial reduction in testes, pressure. Studies confirmed that rutins are potent epididymides weight, and sperm parameters (39). The antioxidants that combat free radicals. Akondi et al. (48) findings are consistent with past work by Etta et al. (40), found that rutin has shown protective effects on sperm which stated that the extract of Phyllanthus amarus against gentamycin, affecting sperm development, affects the count, morphology, and motility of epididymal ototoxicity, and nephrotoxicity. In another study, rutin

346 Mal J Med Health Sci 17(SUPP3): 343-350, Jun 2021 mediated GSH and GSH-Px activities to blockade enhance sperm motility, viability, the integrity of plasma against oxidative stress in rats by elevating testicular membrane and acrosome, condensation of chromatin, GSH-peroxidase and GSH activities (49). and mitochondrial function during cryopreservation Furthermore, Mehfooz et al. (50) revealed that rutin (62). significantly decreases the adverse effects of restraint Diao et al. (63) stated that progesterone-induced sperm stress by inducing the production in testes of cleaved motility and acrosome reactions were improved by PARP1 and cleaved Caspase-3. Other findings by quercetin in male sperm leukocytospermia. Karabulut et Jahan et al. (51) showed that the effect of cisplatin on al. (64) reported that quercetin enhanced sperm motility cellular damage and sperm parameters in male rats in asthenozoospermia cases. In other notes, quercetin was alleviated by rutin co-therapy. Jamalan et al. (52) treatment corrected the degree of male sexual activity illustrated the impact of rutin treatment on the metals’ and improved sperm parameters in rats with diabetes adverse effects on sperm motility. Daim et al. (53) (56). Mehranjani (65) observed that quercetin could reported that animals’ co-treatment with rutin enhances eliminate dexamethasone’s adverse effects on sperm spermatogenesis, sperm count, motility, viability, and and biochemical parameters in mice. morphology. Interestingly, a study by Elsawy et al. (54) showed that rutin reversed the impaired sperm quality c. β-Sitosterol caused by CCl through a decrease in the levels of sperm ϐ-Sitosterol is one of the phytosterols with similar production-related4 hormonal mediators, including chemical structures to that of cholesterol. It is white, serum testosterone, LH, and FSH. dry, and waxy with a distinctive odor. Moreover, Other results indicated that the mitochondrial activity, β-Sitosterol is alcohol-soluble and hydrophobic. which correlated with sperm motility maintenance, was β-Sitosterol demonstrated aphrodisiac ability in a study stabilized and prevented following rutin administration using sexually naive rats (66). Another study reported (55). There is a significant improvement in male sexual significant improvements in sperm viability, growth, activity and sperm parameters of the diabetic animal spermatogonium, fertility index, litter size, Leydig cells, models after five weeks of intervention with rutin. Rutin and spermatozoa in essential oils containing β-sitosterol was also attenuated by impaired serum testosterone and (67). penile cGMP content, improved sexual functionality, and protected against diabetic-induced testicular injury (56). Taken together, the outcomes from Jianhua CONCLUSION et al. (57) revealed that rutin alleviates H2O2-induced oxidative damage and apoptosis in Leydig cells by In conclusion, Phyllanthus plants possessed many stimulating PI3K/Akt signal pathways and helping to beneficial effects on male and female reproductive reduce oxidative stress associated with male infertility. functions and fertility. Despite the limited studies available and the challenges with human intervention b. Quercetin treatments, there is a presumption that Phyllanthus plants The permeability of the blood vessels, including will benefit from human intervention trials, especially capillaries, can be improved and modulated by on reproductive health, thus reflect a potential being quercetin. This compound has anti-aggregant, anti- used as a nutraceutical. Therefore, additional studies cancer, anti-fungal, anti-glaucoma, anti-inflammatory, are needed to fully understand the mechanisms and antioxidant, antiseptic, and antispasmodic activities. complicated relationship between Phyllanthus active Moretti et al. (58) have confirmed that quercetin’s compounds with all reproductive parameters and other protective capacity for sperm motility and viability systems to corroborate any possible health benefits against lipid peroxidative damage in human ejaculated and adverse effects. Furthermore, more outcomes from semen caused by tert-butyl hydroperoxide (TBHP). pharmacological screenings, phytochemical studies, Mazroa (59) also demonstrated the protective effects of clinical studies, and epidemiological data are essential quercetin against BPA-induced damage on sperm and to confirm a substantial connection between the usage cauda. Another finding indicates that quercetin therapy and health benefits of Phyllanthus plant extracts and significantly reduced MDA production and mediated to promote conventional uses, and to establish leading the detrimental effects of metals on sperm (52). compounds. Quercetin showed scavenger properties and a protective effect on human sperm against ultrastructural damage REFERENCES of lipid peroxidase, according to Mazzi et al. (58). Besides, quercetin inhibits the wobble of goat sperm 1. XinMao, Ling-Fang Wu, Hong-Ling Guo, Wen-Jing in frozen semen experiments and increases linearity Chen, Ya-Ping Cui, Qi Qi, Shi Li, Wen-Yi Liang, and straightness (60), enhances sperm motility and Guang-Hui Yang, Yan-Yan Shao, Dan Zhu, Gai-Mei viability, decreases DNA fragmentation, and reduces She, Yun You and L-ZZ. The Genus Phyllanthus: the concentration of ROS in cryopreserved human An Ethnopharmacological, Phytochemical, semen (61). 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