Phytochemistry and ethnomedicinal qualities of metabolites from Phyllanthus emblica L.:A review

Phyllanthus emblica or Indian gooseberry is an integrated part of Ayurvedic and Traditional Chinese Medicines.For several decades,the well-known ancient herb has been extensively utilized in traditional medicine to cure diseases like fever,diabetes,constipation,jaundice,ulcers,biliousness,anemia,anorexia,and dyspepsia.In the traditional system,Indian gooseberry has various ethnomedicinal applications.In the Ayurvedic system,different methods of administration(anupan)have shown different ethnomedicinal properties of Indian gooseberry.Seventy well-known chemical components in Indian gooseberry have been identified through phytochemical evaluation,among which the flavonoids and phenols are most prominent.From the toxicity perspective,it is considered a safe herb in India,and is taken as a food supplement in European countries.The wide-spectrum pharmacological activities of the crude extracts and isolates of Indian gooseberry are attributed to the predominance of phenols and flavonoids.Thus,it is important to study the exact mechanism of the activity of the phytochemicals in Indian gooseberry,especially in anti-cancer activities.Extract of Indian gooseberry enhances proliferation in several cancer cells in vitro,including stem cells like ovarian cancer(OC)cells,and also has been observed to possess anti-proliferative characteristics in vivo.This review intends to explore the therapeutic potential of Indian gooseberry based on scientific reports and attempts to find the gaps for future research.

Two pyrrole acids isolated from Phyllanthus emblica L.and their bioactivities

An undescribed pyrrole acid,1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid(1)and one known pyr-role acid(2)were isolated from the fruits of Phyllanthus emblica.The structures of these compounds were elucidated via the comprehensive analyses of IR,HRESIMS,1D and 2D spectroscopic data.A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide(NO),interleukin-6(IL-6),monocyte chemotactic protein 1(MCP-1)and tumor necrosis factor-α(TNF-α)by reducing the phosphorylation of extracellular regulated protein kinases(ERK)and c-Jun N-terminal kinases(JNK)in RAW 264.7 cells.Additionally,compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.

Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents:Doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells

AIM: To examine the growth inhibitory effects of Phyllanthus emblica (P. emblica) and Terminalia bellerica (T. bellerica) extracts on human hepatocellular carcinoma (HepG2), and lung carcinoma (A549) cells and their synergistic effect with doxorubicin or cisplatin. METHODS: HepG2 and A549 cells were treated with P. emblica and T. bellerica extracts either alone or in combination with doxorubicin or cisplatin and effects on cell growth were determined using the sulforhodamine B (SRB) assay. The isobologram and combination index (CI) method of Chou-Talalay were used to evaluate interactions between plant extracts and drugs. RESULTS: P. emblica and T. bellerica extracts demonstrated growth inhibitory activity, with a certain degree of selectivity against the two cancer cell lines tested. Synergistic effects (CI < 1) for P. emblica /doxorubicin or cisplatin at different dose levels were demonstrated in A549 and HepG2 cells. The T. bellerica/ cisplatin or doxorubicin also showed synergistic effects in A549 and HepG2 cells. In some instances, the combinations resulted in antagonistic effects. The dose reduction level was different and specific to each combination and cell line. CONCLUSION: The growth inhibitory activity of doxorubicin or cisplatin, as a single agent, may be modified by combinations of P. emblica or T. bellerica extracts and be synergistically enhanced in some cases. Depending on the combination ratio, the doses for each drug for a given degree of effect in the combination may be reduced. The mechanisms involved in this interaction between chemotherapeutic drugs and plant extracts remain unclear and should be further evaluated.

Phyllanthuse emblica polyphenols:Optimization of high-voltage pulsed electric field assisted extraction,an antioxidant and anti-inflammatory effects in vitro

Background:The polyphenols extraction of Phyllanthus emblica is primarily carried out using organic solvents,and assisted by physical fields such as ultrasound and microwave for extraction.High voltage pulsed electric field technology(PEF)is a non-thermal processing technology that has high efficiency and minimal damage to thermosensitive substances.PEF has been applied to plant extraction in many studies,however,the extraction of polyphenols from Phyllanthus emblica using the PEF has still not been reported;Objective:This study explores the optimal extraction process of polyphenols from Phyllanthus emblica using the PEF,and investigates its relaxation and anti-wrinkle based on anti-oxidation and anti-inflammatory experiment,in order to develop a Phyllanthus emblica extract with substantial efficacy;Materials and Methods:The method of Phyllanthus emblica extract using PEF is established,and compared with a traditional extraction method.The experimental conditions,such as electric field intensity(0.5–6.0 kV/cm),pulse times(20−120),extraction time(0–60 min)and material concentration(0.5%∼3%),are investigated and optimized using orthogonal experiments;Results:the polyphenols in the Phyllanthus emblica extract were highest at the electric field intensity of 5 kV/cm,120 pulses,extraction time of 30 min,and 2%material concentration.The PEFcontained more polyphenols than the conventional water extraction and ultrasound-assisted extraction.The Phyllanthus emblica extract had substantial antioxidant and anti-inflammatory effects,with a good clearance effect on DPPH(IC50 of 1.82%)and ABTS(IC50 of 1.80%)radicals.At the Phyllanthus emblica extract concentration of 1.25%,inflammatory factors(TNF-α)were reduced by 47.08%;and Conclusion:The PEF is a leading-edge and promising method for preparing Phyllanthus emblica extracts.

Phyllanthus emblica Linn.fruit extract potentiates the anticancer efficacy of mitomycin C and cisplatin and reduces their genotoxicity to normal cells in vitro

Objective： Fruit of Phyllanthus emblica Linn. （PE） is widely consumed as a functional food and used as a folk medicine due to its remarkable nutritional and pharmacological effects. Mitomycin C （MMC） and cisplatin （cDDP） are the most widely used forms of chemotherapeutic drug, but their clinical use is limited by their genotoxicity to normal cells. We aimed to determine whether PE has potential to reduce the genotoxicity, while improving the anticancer effect, of MMC and cDDP. Methods： Cell proliferation was evaluated using the trypan blue exclusion assay and colony-forming assay. Genomic instability （GIN） was measured using the cytokinesis-block micronucieus assay. Results： Co-treatment （72 h） with PE at 20-320 μg/ml significantly enhanced the efficacy of MMC （0.05 μg/ml） and cDDP （1 μg/ml） against Colo205 colorectal cancer cells （P〈0.05）, and at 80-320 μg/ml significantly decreased MMC- and cDDP-induced GIN and multinucleation in normal colonic NCM460 cells （P〈0.05）. PE significantly decreased the mitotic index （P〈0.01）, blocked mitotic progression （P〈0.05）, and promoted apoptosis （P〈0.01） in MMC- and cDDP-treated NCM460 cells, suggesting that PE-mediated inhibition of mitosis and induction of apoptosis may limit the division and survival of highly damaged cells. Also, PE was found to inhibit the clonal expansion of MMC- and cDDP-treated NCM460 cells （P〈0.05） and decrease the heterogeneity of the surviving clones. Conclusions： PE potentiates the anticancer efficacy of MMC and cDDP, while preventing their genotoxicity and inhibiting clonal expansions of unstable genomes in normal cells. These data suggest that PE has the potential to reduce the risk of secondary cancers induced by chemotherapeutics.

Efficacy and safety of Amla(Phyllanthus emblica L.) in non-erosive reflux disease:a double-blind,randomized,placebo-controlled clinical trial

Background： Gastroesophageal reflux disease （GERD） is one of the most common gastrointestinal com- plaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types： erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease （NERD）. GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeco- nomic and therapeutic burdens to both patients and society. Objective： Due to the failure of the conventional treatments for GERD and to the traditional use of Amla （Phyllanthus emblica L.）, in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. Design, setting, participants and interventions： We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD （heartburn, regurgitation and epigastralgia） for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. Main outcome measures： The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Results： Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention （P 〈 0.001）. Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgita- tion severity and heartburn severity during the study period, compared with the placebo group （P 〈 0.001 ）. Conclusion： This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

Phyllanthus emblica leaf extract ameliorates testicular damage in rats with chronic stress

Stress affects the male reproductive system and can cause sub-fertility or infertility. Although Phyllanthus emblica L.(PE) extract has been shown to have high antioxidant capacity and protective properties in damaged tissue, the preventive effects of PE extract on testicular function from stress-related impairment have never been demonstrated. This study aimed to investigate the effects of PE aqueous leaf extract on testicular impairment and protein marker changes in rats suffering from chronic stress. Adult male rats were divided into four groups: a control group, a chronic stress(CS) group, and two groups with CS that received different doses of PE extract(50 or 100 mg/kg body weight(BW)). In the treatment groups, the animals were given PE extract daily before stress induction for 42 consecutive days. Stress was induced through immobilization(4 h/d) followed by forced cold swimming(15 min/d). Sperm quality and the histology of the testes and caudal epididymis were examined, as were levels of serum corticosterone, testosterone, and malondialdehyde(MDA). The expressions of testicular steroidogenic acute regulatory(StAR) and tyrosine-phosphorylated proteins were investigated using immuno-Western blot analysis, as these proteins are assumed to play important roles in spermatogenesis and androgen synthesis. The results showed that PE(50 mg/kg BW) significantly increased sperm concentration and testosterone levels, while decreasing corticosterone levels, MDA levels, sperm head abnormalities, and acrosome-reacted sperm in CS rats. In addition, PE at both doses was found to diminish testicular histopathology in the CS rats. We also found that 50 mg/kg BW of PE significantly improved StAR protein expression and altered the intensities of some tyrosine-phosphorylated proteins in testis. We conclude that PE leaf extract at 50 mg/kg BW can prevent testicular damage in rats with CS.

Effects of 1,2,4,6-tetra-O-galloyl-β-D-glucose from P. emblica on HBsAg and HBeAg Secretion in HepG2.2.15 Cell Culture

A polyphenolic compound, 1,2,4,6-tetra-O-galloyl-β-D-glucose （1246TGG）, was isolated from the traditional Chinese medicine Phyllanthus emblica L. （Euphorbiaceae） and assayed for its potential as an anti-hepatitis B virus （HBV） agent. The cytotoxicity of 1246TGG on HepG2.2.15 as well as HepG2 cells was determined by observing cytopathic effects, and the effects of 1246TGG on secretion of HBsAg and HBeAg in HepG2.2.15 cells were assayed by enzyme immunoassay. Results indicates that treatment with 1246TGG （6.25 ~tg/mL, 3.13 ~tg/mL）, reduced both HBsAg and HBeAg levels in culture supernatant, yet the inhibitory effects tend to decline with the assay time. This study provides a basis for further investigation of the anti-HBV activity and possible mechanism of action of 1246TGG

Phyllanthi Fructus:A modal medicinal and food homologous item in quality evaluation

Phyllanthi Fructus is a highly unique medicine and food homologous item,which exhibits distinctive flavor,notable nutritional value,and abundant pharmacological activity.It has enormous potential in the creation of health products and pharmaceuticals.However,due to the unique laws of quality formation and transfer of Phyllanthi Fructus,its appearance,shape,chemical compositions,nutrients,and sensory flavors are frequently greatly influenced by botanical resources,the processing and storage conditions.As a result,the current quality evaluation model is difficult to meet the needs of Phyllanthi Fructus as a medicine and food homologous item in the development of diversified products.This paper constructs the hierarchical utilization mode of Phyllanthi Fructus based on its unique quality formation and transmission laws,explores the quality evaluation model for food-oriented use and medicinal-oriented use,respectively,and systematically describes the quality evaluation idea under diversified application scenarios.This paper aims to serve as a reference for the construction of a quality evaluation model suitable for the medicine and food homologous item of Phyllanthi Fructus.

3个余甘子种源幼苗干旱胁迫盆栽试验

以海南、福建、广东3个余甘子(Phyllanthus emblica L.)种源为试验材料,采用盆栽法,以土壤相对含水量75%~80%为对照(CK),设置轻度干旱60%~65%、中度干旱45%~50%、重度干旱30%~35%共3个处理,测定对不同种源干旱胁迫下叶绿素含量、苗高和地径的影响。结果表明,不同干旱程度对余甘子均造成了掉叶、叶尖发黄、枯萎等现象,其中广东种源还出现了死亡现象;不同干旱胁迫下,海南种源叶绿素含量、苗高、地径均为最高,轻度干旱胁迫下广东种源叶绿素含量与其他2个种源差异显著;综合考虑,在海南干旱地区绿化及盆栽种源选择均可以使用海南种源,其成活率及生长状况相对较好。

Scientific Validation of the Ethnomedicinal Properties of the Ayurvedic Drug Triphala:A Review

Triphala, a herbal formula composed of the three fruits of Terminalia chebula Retz. （Haritaki, Family： Combretaceae）, Terminalia bellirica Roxb. （Bibhitaki, Family： Combretaceae） and Phyllanthus emblica Linn. or Emblica officinalis Gaertn. （Amalaki or the Indian gooseberry, Family： Euphorbiaceae） is considered to be a universal panacea in the traditional Indian system of medicine the Ayurveda. It has been described in the Ayurveda text as a ＂Ftasayana＂ and to rejuvenat the debilitated organs. Ayurvedic physicians use Triphala for many ailments but most importantly to treat various gastrointestinal disorders. Scientific studies carried out in the past two decades have validated many of the ethnomedicinal claims and researches have shown Triphala to possess free radical scavenging, antioxidant, antiinflammatory, antipyretic, analgesic, antibacterial, antimutagenic, wound healing, anticariogenic, antistress, adaptogenic, hypoglycaemic, anticancer, chemoprotective, radioprotective and chemopreventive effects. Clinical studies have also shown that Triphala was found to have good laxative property, to improve appetite and reduce gastric hyperacidity. Studies have also shown that Triphala was effective in preventing dental caries and that this effect was equal to that of chlorhexidine. The current review addresses the validated pharmacological properties of Triphala and also emphasizes on aspects that need further investigation for its future clinic application.