The development of Terminalia chebula Retz.(Combretaceae) in clinical research

Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization.Terminalia chebula Retz.(Fam.Combretaceae),is called the‘King of Medicine??in Tibet and is always listed at the lop of the list of‘Ayurvedic Materia Medica??because of its extraordinary power of healing.The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings.Some of the folklore people used this plant in the treatment of asthma,sore throat,vomiting,hiccough,diarrhea,dysentery,bleeding piles,ulcers,gout,heart and bladder diseases.The plant has been demonstrated to possess multiple pharmacological and medicinal activities,such as antioxidant,antimicrobial,antidiabetic,hepatoprotective,anti-inflammatory,antimutagenic,antiproliferative,radioprotective,cardioprotective,antiarthritic,anticaries,gastrointestinal motility and wound healing activity.But no systematic updated information on the therapeutic effectiveness of Terminalia chebula,a popular herbal remedy in India and South-East Asia has so far been reported.This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz.and some of its isolated compounds,along with their safety evaluation.This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.

Evaluation of Analgesic and Anti-Inflammatory Activities on Ethanolic Extract of <i>Terminalia chebula</i>Fruits in Experimental Animal Models

The present study was undertaken to evaluate the analgesic and anti-inflammatory activities of ethanolic extract of Terminalia chebula (commonly known as Haritaki) fruits in experimental animal models. The study was carried out using Swiss Albino mice (20-25 g) and Long Evans rats (100-150 g) of either sex. The analgesic activity of Terminalia chebula was assessed by using hot plate method. For the determination of analgesic effect, doses of ethanolic extract of Terminalia chebula used in the present study were 250 mg/kg and 500 mg/kg body weight (BW). Anti-inflammatory effect was analyzed by carrageenan induced paw edema method with the administration dose of 300 mg/kg BW of animals. The analysis of experimental data was performed by statistical process of ANOVA to determine the variability of sample, while Dunnet’s test was performed for evaluation of comparative analgesic and anti-inflammatory activity of Terminalia chebula with control and standard. The animals were divided into four treatment groups of six animals each and the “Mean ± SEM” is the statistical identifiable value of the data and P values <0.05 was considered statistically significant. Hot plate test showed a significant increase in the mean reaction time to heat stimuli in hot plate method at both 250 mg/kg and 500 mg/kg BW doses throughout the observation period in 30 minutes and 60 minutes after treatment, which was comparable to the standard ketorolac and control group. In carrageenan induced paw edema method, considerable results were found after determining the percentage change in paw volume in extract. In both cases of analgesic and anti-inflammatory study, % inhibition of pain and inflammation were evaluated. Comparing with control, largest inhibition was found in inhibiting inflammation 5 hours after treatment, while the largest inhibition of pain was obtained in 30 minutes and 60 minutes after treatment of doses. The present study suggests that ethanolic extract of Terminalia chebula fruits has significant analgesic and anti-inflammatory activities.

UPLC-Q/TOF-MS based metabonomics revealed protective effect of Terminalia chebula extract on ischemic stroke rats

Terminalia chebula(TC),a kind of Combretaceae,is a widely used herb in India and East Asia to treat cerebrovascular diseases.However,the potential mechanism of the neuroprotective effects of TC at the metabonomics level is still not unclear.The present study focused on the effects of TC on metabonomics in stroke model.In our study,rats were divided randomly into Sham,Model,and TC groups.The TC group were intragastricly administered with TC for 7 d after middle cerebral artery occlusion(MCAO)operation.The sham and the model groups received vehicle for the same length of time.Subsequently,the neuroprotective effects of TC were examined by neurological defects evalua⁃tion,infarct volume assessment,and identification of biochemical indicators for antioxidant and anti-inflammatory activi⁃ties.Further,metabonomics technology was employed to evaluate the endogenous metabolites profiling systematically.Consist to results of biochemical and histopathological assays,pattern recognition analysis showed a clear separation of the Model and the Sham group,indicating a recovery impact of TC on the MCAO rats.Moreover,12 potential biomarkers were identified in MCAO Model group,involved in energy(lactic acid,succinic acid,and fumarate),amino acids(leucine,alanine,and phenylalanine)and glycerophospholipid[PC(16∶0/20∶4),PC(20:4/20:4),LysoPC(18:0)and LysoPC(16:0)]metabolism,and other types of metabolism(arachidonic acid and palmitoylcarnitine).Notably,we found that metabolite levels of TC group were partially reversed to normal.In conclusion,TC could ameliorate MCAO rats by intervening with energy metabolism(glycolysis and TCA cycle),amino acid metabolism,glycerophospholipid metabolism and other types of metabolism.

Analgesic Activities of Methanol Extract of <i>Terminalia chebula</i>Fruit

Pain is a sensation which in many cases represents the only symptom for the diagnosis of several disorders. Throughout ages man has used many different remedies for pain relief, among which medicinal herbs are most common due to their efficacy and relative safety due to their natural origin. In present study methanol extract of Terminalia chebula fruit was evaluated for its analgesic effects in albino mice. The extract was prepared using whole dried powdered fruit with seeds in absolute methanol. It was then subjected to rotary evaporator under reduced pressure to get concentrated extract;different doses (300, 500 and 1000 mg/kg) were assessed for analgesic activity by tail immersion technique and acetic acid induced writhing test. Similar doses of Aspirin were used as standard drug (positive control) for comparison. Results of both tail flick method and acetic acid induced writhing test revealed that T. chebula fruit extract possessed varying degree of analgesic activity significant at 300 mg/kg and highly significant at 500 and 1000 mg/kg in comparison to control. The results were almost similar to standard drug. In acetic acid induced writhing test, maximum inhibition of writhing was observed at 1000 mg/kg where the number of writhes decreased from 14.1 to 5.2 indicating 63.1% inhibition. Above findings suggest that T. chebula fruit extract possesses significant analgesic activity in albino mice with reference to positive and negative control groups;however further studies on a large number of animals with clinical trials are required to confirm safe and effective use of this fruit extract in humans for analgesic purpose.

Termitomenins F and G,Two New Lignan Glucosides from Terminalia chebula var.tomentella(Kurz)C.B.Clarke

The extensive chemical investigation on the branches and leaves of Terminalia chebula var.tomentella(Combretaceae)led to the isolation of two new lignan glucosides with a furofuran skeleton,termitomenins F(1)and G(2).In addition,19 known compounds including five lignan glucosides(3-7),six hydrolyzable tannins(8-13)and eight simple phenolics(14-21)were also identified.Their structures were determined by comprehensive spectroscopic analyses.It is noted that 8 and 9 were C-glycosidic hydrolyzable tannins with one hexahydroxydiphenoyl and one gallagyl group linked to an open-chain glucosyl C-1/O-2/O-3 and O-4/O-6,respectively,which were rarely found in plants.Nine known compounds,6-9,13,and 18-21,were procured from the titled plant for the first time,while 3-5,10-12 and 14-17 were also found in the fruits.Notably,the known hydrolyzable tannins 8-13 exhibited strongerα-glucosidase inhibitory activities with IC_(50) values ranging from 0.10 to 3.12μM,than the positive control,quercetin(IC_(50)=9.38±0.33μM).

A New Record on Flowering in Harar (<i>Terminalia chebula</i>Retz.) Seedling

Harar (Terminalia chebula), a large deciduous tree belongs to family combretaceae. It grows naturally in greater part of India up to 1500 m elevation. Due to several alkaloids present in fruit, it is used as laxative, purgative and astringent for curing a number of ailments. Keeping in view its medicinal and tanning properties, the authors have been working for the last two decades on various aspects like propagation and development of promising strains of harar. Grafting/budding techniques have been standardized to produce true to type precocious plants which bear flower in two to three years. However, flowering has been observed in three months old seedling, which can be ascribed to biochemical and/or cellular changes. Early flowering is a rare incidence in tree seedlings which otherwise could be very useful for breeding and early evaluation of fruit species.

<i>In vitro</i>Antibacterial Activity of Bioactive Potent Compounds from <i>Terminalia chebula</i>against Some Common Human Pathogens

Objective: Emergence of community-acquired infections due to multi drug resistant (MDR) common human pathogens have caused a great problem to clinicians and this directed us to search systematically for a different remedy with compounds particularly from plant origin. Methods: The antibacterial activity was evaluated using agar well diffusion assay method against some common gram positive and gram negative bacteria. Results: In vitro study with Terminalia chebula Retz. (Combretaceae) stem bark extracts, eight isolated triterpenoids and four triterpenoid derivatives were found to be effective against Bacillus subtilis, Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa and Escherichia coli. Conclusions: Pure compounds from T.chebula could be effectively used as antibacterial agents if it is possible to develop the molecules synthetically. At the same time crude extracts with specified active principles could also be used and/or introduced in Traditional Medicine/Complementary Alternative Medicine (TM/CAM) as antibacterial into National/International Health Systems as per the guideline of Ayurvedic formularies.

Effect of Terminalia chebula Retz. extraction with water on Staphylococcus epidermidis activity and its biofilm formation

Background:Based on modern pharmacological studies,Terminalia chebula Retz.exhibits antimicrobial activity against a variety of bacteria.Previously,we found Terminalia chebula Retz.exhibited excellent antibacterial activity against Malassezia restricta.Methods:We determined the minimal inhibitory concentration(MIC)and minimum bactericidal concentration of Terminalia chebula Retz.extraction with water(TRW)against Staphylococcus epidermidis(including Staphylococcus epidermidis 1-15)using the microdilution method.Staphylococcus epidermidis 1(SE11),which was the most sensitive to TRW,was selected as the test bacterium for subsequent experiments.The time-kill curve of TRW on SE11 was generated using the viable count method.Further,an in vitro biofilm model of SE11 was constructed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide test,semi-quantitative crystal violet experiment,and scanning electron microscopy.The effects of TRW on the total amount of biofilm formation,the number of viable biofilm bacteria,and biofilm microstructure of SE11 were also determined using a semi-quantitative crystal violet experiment,viable count method,and scanning electron microscopy.Finally,the electrical conductivity and soluble protein content of the SE11 suspensions were determined.Results:The average MIC of TRW against SE11 was 0.75±1.09 mg/mL.TRW(1/2MIC and 2MIC)and zinc pyrithione(1/2MIC and 2MIC)had no significant effect on total biofilm inhibition in the adhesion stage(P>0.05)and the aggregation stage(P>0.05).Further,TRW(1/2MIC and MIC)and zinc pyrithione(1/2MIC and MIC)had no significant effect on viable biofilm bacteria in the adhesion stage(P>0.05)and aggregation stage(P>0.05).TRW destroyed the integrity of the SE11 cell membrane,resulting in leakage of intracellular substances.Conclusion:TRW inhibits SE11 biofilm formation and is similar to zinc pyrithione in the adhesion and aggregation stages,which provides a theoretical basis for its application in the field of antimicrobial additives.

Terminalic Acid, a New Tannin from the Fruit of Terminalia chebula

Terminalic acid 1, a new hydrolysable tannin, was isolated from the fruit of Terminalia chebula. Its structure was found to be 1-O-galloyl-2,4-chebuloyl-beta-D-glucopyranose by chemical method and H-1-NMR, C-13-NMR, H-1-H-1 COSY, HMQC, HMBC and FAB-MS spectral analyses.

Antimicrobial potential of Terminalia chebula Retz. fruit extracts against ear pathogens

AIM: To evaluate the antimicrobial potential of Terminalia chebula(T. chebula) extracts against pathogens causing otitis externa and compare it with ear drops.METHODS: Four different extracts, methanol, ethanol,acetone and aqueous(hot and cold) extracts, from the T. chebula were tested for their antimicrobial activity through the agar well diffusion method and minimum inhibitory concentration(MIC)/minimum bactericidal concentration(MBC) values were determined through the macrodilution broth method against six different microorganism, five bacterial(one gram positive and four gram negative) and one yeast.RESULTS: Organic and aqueous fruit extracts displayed activity against all five tested bacterial ear pathogens with a maximum zone of inhibition of 31.6 mm against Staphylococcus aureus, followed by Acinetobacter sp.(24.6 mm), Pseudomonas aeruginosa(23.6 mm),Proteus mirabilis(21 mm) and Escherichia coli(19.3mm). Of the four solvents evaluated, acetonic fruit extract of T. chebula was found to be best. The MIC values ranged between 0.78 mg/m L and 50 mg/m L for the different bacterial ear pathogens and MBC values ranged between 1.56 mg/m L and 50 mg/m L. The acetonic fruit extract showed larger inhibition zones compared to the herbal ear drops, Kan pip with lowest MIC of 0.78 mg/m L and MBC of 1.56 mg/m L.CONCLUSION: Acetonic extract of T. chebula fruit may be used to treat otitis externa. However, more detailed studies, such as in vivo testing and pharmacokinetics properties, are needed to determine its therapeutic potential.

高效液相色谱法测定诃子中诃黎勒酸和诃子酸

建立高效液相色谱法测定诃子中诃黎勒酸、诃子酸含量的方法,对《中华人民共和国药典》2020年版一部中诃子含量测定项进行补充。采用Dikma Platisil C_(18)色谱柱(250 mm×4.6 mm,5μm)为分析柱,柱温为35℃,以0.1%甲酸水溶液-乙腈-甲醇(体积比为78∶16∶6)作为流动相等度洗脱,流量为1 mL/min,进样体积为5μL,检测波长为280 nm。诃黎勒酸、诃子酸的质量分别在0.03203~1.025μg、0.03555~1.137μg范围内与色谱峰面积线性关系良好,相关系数分别为0.9996、0.9995,方法检出限分别为2.67、4.44 ng,定量限分别为8.00、11.85 ng。测定值的相对标准偏差分别为1.9%、1.8%(n=6),样品加标平均回收率分别为99.0%、99.2%。该方法可用于诃子药材的质量控制方法。

高效液相色谱指纹图谱结合一测多评法评价诃子药材质量

目的评价诃子药材的质量。方法建立诃子药材的高效液相色谱指纹图谱,采用相似度计算、聚类分析和主成分分析法对其质量进行评价。以柯里拉京为内参物,建立测定诃子药材中莽草酸、没食子酸、没食子酸甲酯、没食子酸乙酯、诃黎勒酸、鞣花酸、诃子酸含量的一测多评法,并将计算结果与外标法测定结果进行比较。结果18批诃子药材的指纹图谱有23个共有峰,指认出2号峰为莽草酸、7号峰为没食子酸、11号峰为没食子酸甲酯、14号峰为柯里拉京、15号峰为没食子酸乙酯、16号峰为诃黎勒酸、20号峰为鞣花酸、22号峰为诃子酸,相似度均大于0.95。聚类分析结果显示,18批诃子药材聚为2类,其中产地为青海的2批药材聚为一类,其余药材聚为一类。主成分分析结果显示,主成分特征值大于1的5个成分累积方差贡献率为84.088%。采用一测多评法计算的18批诃子药材中莽草酸、没食子酸、没食子酸甲酯、没食子酸乙酯、诃黎勒酸、鞣花酸、诃子酸的含量与外标法测定结果无显著差异(P>0.05)。结论高效液相色谱指纹图谱结合一测多评法可有效评价诃子药材的质量。

ICP-MS测定诃子炮制前后无机元素含量及安全性评价

目的:建立诃子生品及清炒、麸煨、砂烫、烘制4种炮制品中26个无机元素的分析方法,对其中重金属及有害元素进行健康风险评估。方法:采用电感耦合等离子体质谱法,以铑和铼为内标,通过标准曲线法测定诃子中的26个元素;采用危害指数(HI)法和暴露限值(MOE)法进行健康风险评估。结果:26个元素的标准曲线线性关系良好,仪器检出限为0.0002~0.4342μg·kg^(-1),加样回收率为83.21%~116.84%。诃子炮制前后无机元素差异明显,部分重金属及有害元素所致健康风险较低。结论:该方法简便、准确,适用于诃子中无机元素的含量测定,为其重金属及有害元素健康风险评估提供了参考。

诃子在藏药炮制中的应用

通过查阅近年来国内外文献,归纳、分析了诃子在藏药炮制中的应用以及诃子炮制一些矿物药和有毒植物药过程的研究进展,根据诃子化学成分推测诃子炮制铁粉、草乌的原理及减毒机制,为进一步深入探讨藏药诃子炮制矿物药、有毒植物药的机制提供参考。

7种诃子多酚透皮吸收试验研究

考察诃子中7种多酚类成分透皮吸收性能,研究不同透皮吸收促进剂对诃子中7种多酚类成分体外透皮吸收的影响。以30%乙醇生理盐水为接受液,以SD大鼠皮肤为渗透屏障,采用改良Franz扩散池法对诃子多酚体外经皮扩散情况进行测定,并选择零级动力学模型、一级动力学模型和Higuchi方程模型对曲线进行拟合分析,测定取样末点诃子中7种多酚类成分的皮肤滞留量。诃子次酸、没食子酸、安石榴苷、柯里拉京、诃黎勒酸、鞣花酸、诃子酸的单位面积累计透皮量为7.348、16.68、19.96、22.90、3.548、0.5336、7.733 mg/cm^(2),皮肤蓄积率为0.36%、0.76%、1.85%、1.38%、2.56%、0.63%、3.79%。比较不同浓度的氮酮、丙二醇对7种诃子多酚的体外透皮吸收的影响,发现以1%丙二醇作为促进剂时可有效促进诃子多酚体外透皮吸收,氮酮作为透皮吸收促进剂可减弱诃子多酚体外透皮吸收,增大皮肤滞留量。

Enhanced Antioxidant Capacities in vivo Caused by the Change in Key Constituent of Terminalia chebula Retz. Treated with Tibet Traditional Process

In order to investigate the chemical-biological relationship caused by the special processing technology,the constituent＇s content and antioxidant capacity in vivo of Euphorbia fischeriana Steud processing Terminalia chebula Retz. have been tested. Taking T. chebula Retz. as control,the content of gallic acid is analyzed with high performance liquid chromatography（HPLC） method. The results show that the increase of gallic acid concentration from 4.54% to 7.46% leads to enhancement of the antioxidant capacities in vivo of the E. fischeriana Steud processing T. chebula Retz. The significant antioxidant capacity in vivo（p〈0.05） of the processed product possesses is better than the unprocessed herb. Its superoxide dismutase（SOD）and malondia-ldehyde（MDA） contents in serum,the MDA content in liver can match the effects of vitamine E when administered at high dosage.

诃子基原物种及其混伪品的形态鉴别与分子鉴定

目的:建立能够准确鉴别诃子、绒毛诃子及其混伪品的分子鉴定方法。方法:对诃子、绒毛诃子及其混伪品的新鲜果实进行烘干,观察其干燥前后的形态;提取样品DNA,采用DNA条形码内转录间隔区2(ITS2)序列和psbA-trnH序列进行聚合酶链式反应扩增并测序,采用DANMAN 7、MAGE 6软件对测序结果进行序列比对,计算Kimura 2-paramete遗传距离,并构建邻接法系统发育树。结果:形态观察发现,诃子、绒毛诃子果实干燥前后与混伪品有较大的差异,可以通过形态差异进行鉴别;DNA条形码序列表明,诃子和绒毛诃子ITS2序列基本一致,仅发现4个单核苷酸多态性位点,但不能由此对两者进行区分;诃子和绒毛诃子的psbA-trnH序列存在2处明显差异,可对两者进行准确区分;绒毛诃子中存在2种类型的单倍型,其明显差异在于是否在psbA-trnH序列上存在1段16 bp的串联重复序列;混伪品与诃子、绒毛诃子之间具有较大的psbA-trnH序列差异,可直接在美国国家生物技术信息中心比对进行区分;对市场上流通的诃子炮制品进行鉴定发现,其多为2种单倍型绒毛诃子,且存在毛诃子混伪的情况。结论:利用psbA-trnH序列可准确鉴别诃子、绒毛诃子及其混伪品,发现绒毛诃子中存在2种类型的单倍型。

藏药阿如久巴丸质量标准研究谢平次仁旺姆杨丽琼达娃卓玛

目的:修订提高阿如久巴丸的质量标准。方法:参照《中国药典》2020版四部通用检测方法分别测定了阿如久巴丸的水分、总灰分、酸不溶性灰分、浸出物;采用薄层色谱法(TLC)对阿如久巴丸中诃子、红花进行定性鉴别。结果:阿如久巴丸中诃子、红花的薄层色谱斑点清晰,分离度好;阿如久巴丸药材的水分含量平均值为6.99%;阿如久巴丸的总灰分含量平均值为21.43%,建议总灰分不得过26.0%,酸不溶性灰分平均含量为0.296%,建议酸不溶性灰分不得过0.36%;浸出物含量平均值为33.35%,建议浸出物含量不得少于27.0%。结论:所建立的方法操作简便、结果准确,能够用于阿如久巴丸的质量控制。

Potential therapeutic applications for Terminalia chebula in Iranian traditional medicine

Terminalia chebula(family:Combretaceae)is widely used in the traditional medicine of India and Iran to treat diseases that include dementia,constipation,and diabetes.This tree is known in Iranian traditional medicine(ITM)as halileh or halilaj and the fruit is used to develop treatments.It is described in ITM as an astringent that has a"cold"and"dry"temperament.References to the medicinal properties of Terminalia chebula were collected from important ITM sources and from modern medical databases(Pub Med,Scirus,Science Direct,and Scopus).The medicinal properties described for thistree in ITM were compared with those reported in studies of modern phytotherapy.The results confirm that the tree referred to as halileh in traditional books is the Terminalia chebula used in present-day studies.Treatments that have not been evaluated in modern phytotherapy but have been traditionally treated with Terminalia chebula include fever,and psychological and psychiatric issues.This article confirms the medicinal uses of Terminalia chebula.