Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

Alismatis Rhizoma(AR)is widely used in Chinese medicine,and its major bioactive components,triterpenes,reportedly possess various pharmacological activities.Therefore,it is very important to study the metabolism of triterpenes in vivo.However,the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways.In this study,an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method,which was based on the characteristic ions from an established database of known triterpenes,was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts(ARE).As a result,a total of 233 constituents,with 85 prototype compounds and 148 metabolites,were identified for the first time.Hydrogenation,oxidation,sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR.In addition,the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time.Those results provide comprehensive insights into the metabolism of AR in vivo,which will be useful for future studies on its pharmacodynamics and pharmacokinetics.Moreover,this established strategy may be useful in metabolic studies of similar compounds.

Anti‑inflammatory and Cytotoxic Triterpenes from the Rot Roots of Panax notoginseng

Four new protopanaxatriol-type triterpenes(1-2)and glucosides(3-4),were isolated from the rot roots of Panax notoginseng(Burk.)Chen,along with four known ones(5-8).Their structures were elucidated on the basis of extensive spectroscopic analysis(HRESIMS,NMR,UV,IR,and OR)and acidic hydrolysis.The possible transformation pathway of these compounds were also speculated from ginsenoside Rg_(1).Compound 1,with a uniqueα,β-unsaturated ketene in its side chain,showed significant inhibitory effects against NO production on Murine macrophage cells(IC_(50)=4.12±0.20μM)and comparable cytotoxicities against five human cancer cell lines(myeloid leukemia HL-60,lung cancer A-549 cells,hepatocellular carcinoma SMMC7721,breast cancer MCF-7,and colon cancer SW480)to positive control,cisplatin(DDP).

Ganoderma triterpenes slow cyst growth in polycystic kidney disease

OBJECTIVE Autosomal dominant polycystic kidney disease(ADPKD)is a common inherited disease with a high morbidity around 1/1000-1/400,characterized by progressive enlargement of fluid-fil ed cysts derived from renal tubular epithelial cells.Massive cysts gradually compress renal parenchyma destroying normal renal structures and compromising renal functions.Unfortunately,it will cause end-stage renal disease in most of the patients but without effective therapy now,who have to live on hemodialysis or kidney transplantation.Based on this present situation,it is of great significance to find early intervention to inhibit renal cyst development.The projective of this study was to investigate whether Ganoderma triterpenes(GT)can inhibit renal cyst development and study the related mechanism.METHODS and RESULTS First,we used MDCK cyst model,cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells.GT inhibited MDCK cyst formation significantly,and inhibited cyst enlargement dose-dependently proving GT cyst inhibition in vitro.Then we used an embryonic kidney cyst model,wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-c AMP.GT inhibited embryonic kidney cyst development significantly in a dosedependent and reversible manner proving GT cyst inhibition at organ level.Furthermore,we used two ADPKD mouse models with severe cystic kidney disease phenotypes.GT dramatically inhibited renal cyst development,decreased ADPKD mouse kidney volume and the cyst index inside proving GT cyst inhibition in vivo.By Western blot,we proved GT down-regulated Ras/MAPK signal pathway without detectable effect on m TOR signal pathway both in MDCK cells and two ADPKD mouse kidneys.CONCLUSION GT retard renal cyst development both in vitro and in vivo significantly.The related mechanisms were involved in GT promoting renal tubular epithelial cell differentiation,down-regulating intracellular c AMP level and Ras/MAPK signal pathway.

TRITERPENES AND OTHER CONSTITUENTS FROM CYNOMORIUM SONGARICUM

From the whole plant of Cynomorium songaricum a new triterpene was isolated together with acetyl ursolic acid, ursolic acid, β-sitosterol palmitate, β-sitosterol, palmitic acid and β-sitosterol glucoside. The structure of the new compound was elucidated as ursa-12-ene-28-oic acid, 3β-propanedioic acid monoester (cynoterpene, 1).

Two New Pentacyclic Triterpenes from Sabia parviflora

Two new pentacyclic triterpene acids, 1a, 3b-dihydroxyl-olean-12-en-28-oic acid and 1a, 2a, 3b-trihydroxyl-olean-12-en-28-oic acid, were isolated from the arial parts of Sabia parviflora.

Two New Triterpenes from Astilbe chinensis

Two new triterpenoids, 3β, 6β, 24-trihydroxyolean-12-en-27-oic acid and 3β-acetoxy-6β-hydroxyurs-12-en-27-oic acid, as well as three known triterpenoids were isolated from ~e rhizomes of Astilbe chinensis. Their structures were elucidated by spectroscopic methods. These compounds showed Anti-cancer activities.

Comparative genomics reveals the diversification of triterpenoid biosynthesis and origin of ocotilloltype triterpenes in Panax

Gene duplication is assumed to be the major force driving the evolution of metabolite biosynthesis in plants.Freed from functional burdens,duplicated genes can mutate toward novelties until fixed due to selective fitness.However,the extent to which this mechanism has driven the diversification of metabolite biosynthesis remains to be tested.Here we performed comparative genomics analysis and functional characterization to evaluate the impact of gene duplication on the evolution of triterpenoid biosynthesis using Panax species as models.Wefound that whole-genome duplications(WGDs)occurred independently in Araliaceae and Apiaceae lineages.Comparative genomics revealed the evolutionary trajectories of triterpenoid biosynthesis in plants,which was mainly promoted by WGDs and tandem duplication.Lanosterol synthase(LAS)was likely derived from a tandemduplicate of cycloartenol synthase that predated the emergence of Nymphaeales.Under episodic diversifying selection,the LAS gene duplicates produced by g whole-genome triplication have given rise to triterpene biosynthesis in core eudicots through neofunctionalization.Moreover,functional characterization revealed that oxidosqualene cyclases(OSCs)responsible for synthesizing dammarane-type triterpenes in Panax species were also capable of producing ocotilloltype triterpenes.Genomic and biochemical evidence suggested that Panax genes encoding the above OSCs originated from the specialization of one OSC gene duplicate produced from a recent WGD shared by Araliaceae(Pg-b).Our results reveal the crucial role of gene duplication in diversification of triterpenoid biosynthesis in plants and provide insight into the origin of ocotillol-type triterpenes in Panax species.

Triterpenes from the stem bark of Mitragyna diversifolia and their cytotoxic activity

AIM: To study the chemical constituents and bioactivity of the stem bark of Mitragyna diversifolia. METHOD: Compounds were isolated by various chromatographic methods. Their structures were elucidated on the basis of spectroscopic techniques(IR, UV, MS, and NMR), and they were evaluated for their cytotoxic activities by the MTT method. RESULTS: Eight triterpenes were isolated and identified as 3α, 6β, 19α-trihydroxy-urs-12-en-28-oic acid(1), 3β, 6β, 19α- trihydroxy-urs-12-en-28-oic acid(2), 3-oxo-6β-19α-dihydroxy-urs-12-en-28-oic acid(3), 3β, 6β, 19α-trihydroxy-urs-12-en-24, 28-dioic acid 24-methyl ester(4), 3β, 6β, 19α, 24-tetrahydroxy-urs-12-en-28-oic acid(5), rotundic acid(6), 23-nor-24-exomethylene- 3β, 6β, 19α-trihydroxy-urs-12-en-28-oic acid(7), and pololic acid(8), respectively. All of the isolates were tested against two human tumor cell lines, MCF-7(breast) and HT-29(colon). CONCLUSION: Compound 1 was a new triterpene. Compounds 5-7 exhibited potent inhibitory effects on the growth of MCF-7 and HT-29 cells, and the others showed no cytotoxicity.

Tyrosinase Inhibitory Activity of Total Triterpenes and Poricoic Acid A Isolated from Poria cocos

Objective With the improvement of people＇s living standards, people＇s requests for beauty are increasing. Skin whitening and lightening have become the pursuit of many women, and whitening and removing freckles have become the focus of scientific research. At present, widely used whitening agents, such as kojic acid, vitamin C, and its derivatives, have shortcomings such as poor stability and retarded effect. Therefore, safer and more effective whitening products from herbs are urgently needed. To explore the possibility of triterpenes as whitening active substance, the effects of total triterpenes of Poria（TTP） and poricoic acid A（PAA） on mushroom tyrosinase activities and B16 cells were investigated, and their mechanisms on mushroom tyrosinase were also studied. Methods Using arbutin and nicotinamide as reference substances, we determinated the inhibitory effects of TTP and PAA on mushroom tyrosinase and tyrosinase in B16 cells and then studied the inhibitory mechanism on mushroom tyrosinase. Results TTP and PAA exhibited good inhibitory effects on the activities of monophenolase and diphenolase in mushroom tyrosinase, as well as a certain inhibitory effect on tyrosinase in B16 cells. Conclusion TTP and PAA are potential whitening active ingredients.

Immunomodulatory effects and structure-activity relationship of botanical pentacyclic triterpenes:A review

Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as antioxidant,anti-tumor,anti-microbial and anti-inflammatory activities.It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system.Recently,the pharmacological validation on immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity.In this review,we have highlighted several studies on immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models.This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship.Hence,the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial immunomodulatory properties.

Discovery and analysis of a new class of triterpenes derived from hexaprenyl pyrophosphate

Triterpenes are derived from squalene or oxidosqualene.However,a new class of triterpenes derived from hexaprenyl pyrophosphate has been recently discovered,formed by a new family of chimeric class I triterpene synthases.The cyclization mechanisms of triterpenes were elucidated by isotopic labeling and protein structural analyses,which helps understand the biosynthesis of triterpenes in nature.

Protein tyrosine phosphatase 1B inhibitory activities of ursane-type triterpenes from Chinese raspberry, fruits of Rubus chingii

Protein tyrosine phosphatase 1 B(PTP1 B) has led to an intense interest in developing its inhibitors as anti-diabetes, anti-obesity and anti-cancer agents. The fruits of Rubus chingii(Chinese raspberry) were used as a kind of dietary traditional Chinese medicine. The methanolic extract of R. chingii fruits exhibited significant PTP1 B inhibitory activity. Further bioactivity-guided fractionation resulted in the isolation of three PTP1 B inhibitory ursane-type triterpenes: ursolic acid(1), 2-oxopomolic acid(2), and 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid(3). Kinetics analyses revealed that 1 was a non-competitive PTP1 B inhibitor, and 2 and 3 were mixed type PTP1 B inhibitors. Compounds 1-3 and structurally related triterpenes(4-8) were further analyzed the structure-activity relationship, and were evaluated the inhibitory selectivity against four homologous protein tyrosine phosphatases(TCPTP, VHR, SHP-1 and SHP-2). Molecular docking simulations were also carried out, and the result indicated that 1, 3-acetoxyurs-12-ene-28-oic acid(5), and pomolic acid-3β-acetate(6) bound at the allosteric site including α3, α6, and α7 helix of PTP1 B.

Anti-Biofilm, Anti-Quorum Sensing, and Anti-Proliferative Activities of Methanolic and Aqueous Roots Extracts of Carica papaya L. and Cocos nucifera L.

Objective: This study focused on the antibacterial and anti-proliferative activity of extracts from Carica papaya and Cocos nucifera roots. Methodology: The minimum inhibitory concentration and the minimum bactericidal concentration of the extracts on Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, and Staphylococcus aureus were deduced by the microdilution method. The anti-biofilm activity was determined on all four strains and anti-quorum sensing activity by inhibition of violacein production in Chromobacterium violaceum. Anti-proliferative activity on prostate cultured cancer cells was evaluated by MTT assay. Sterols and triterpenes were also assayed in this study. Results: The methanolic extract of Carica papaya showed the best anti-biofilm effect with a percentage inhibition of 66.10 ± 1.79. The methanolic extract of Cocos nucifera had the strongest inhibition on the production of quorum sensing (61.42 ± 0.28). In addition, the methanolic extract of Cocos nucifera roots showed the best cytotoxic effect on prostate cancer LNCaP cell lines (IC50 = 26.98 ± 2.6 μg/mL) and Carica papaya on the PC-3 lines (IC50 = 127.20 ± 5.99 μg/mL). The extracts were also rich in triterpenes and sterols. Conclusion: This study provides support for the ethnomedical use of Carica papaya and Cocos nucifera roots as an antimicrobial and anticancer.

Hepatoprotective properties of oleanolic and ursolic acids in anti-tubercular drug-induced liver damage

Objective:To estimate to what extent the mixture of ursolic acid and oleanolic acid,in addition to the antitubercular standard regime,affects the hepatotoxicity profile.Methods:Liver injury was induced in male BALB/c mice by administering,per os and daily for 11 weeks,a combination of anti-Tubercular(anti-TB) agents Rifampicin(10 mg/kg),Isoniazid(10 mg/kg),and Pyrazinamide(30 mg/kg).The ursolic acid and oleanolic acid mixture at doses of 100 or 200 μg/mouse/day was subcutaneously injected throughout the entire study period(11 weeks).Biochemical and hematological analysis was supplemented by liver histological examination.Results:Animals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.Conclusions:The triterpene mixture is able to prevent the steatosis induced by the anti-TB drugs.

Allelochemicals of Panax notoginseng and their effects on various plants and rhizosphere microorganisms

Panax notoginseng(Araliaceae)is an important ginseng herb with various health benefits and a history of cultivation in southwestern China over 400 years.In recent years?.notoginseng has faced serious continuous-cropping obstacles due to its large-scale cultivation.In this study,we aim to explore the allelochemicals of P.notoginseng and their interactions with various plants and rhizosphere microor-ganisms.The chemical constituents of the soil cultivated with 3-year-old P.notoginseng were studied by column chromatography,spectroscopic and GC-MS analyses.We identified 13 volatile components and isolated six triterpenes(1-4,6-7)and one anthraquinone(5).Compounds 1-7 were tested for their effects on seed germination and root elongation in P.notoginseng,corn,wheat,turnip,water spinach and Arabidopsis thaliana.We also examined the effect of compounds 1-7on the growth of ten rhizosphere microorganisms of P.notoginseng.At a concentration of 1.0 ug mL',compounds 3 and 5-7 caused the death of P.notoginseng root cells and compounds 2,6 and 7 induced the death of root cells of A.thaliana.Compounds 1-5and 7 inhibited elongation of A.thaliana root tip cells at a concentration of 10.0μg mL^-1.Moreover,at a concentration of 0.1 mg mL^-1,compounds 3,4,6 and 7 inhibited the growth of probiotics and promoted the growth of pathogens of P.notoginseng.These results suggest that these isolated ursane-type triterpenoid acids and anthraquinone are potential allelochemicals that contribute to continuous-cropping obstacles of P.notoginseng.

Classification of facial wrinkles among Chinese women

It is generally recognized that Caucasians and Asians have different skin aging features. The aim of this study was to develop a facial wrinkle grading scale for Chinese women. Standard photographs were taken of 242 Chinese women. Six sets of 0 to 9 wrinkle scales with reference photographs and descriptions were selected, including grading scales for resting and hyperkinetic crow＇s feet, frontalis lines, glabellar frown lines, and nasolabial folds. To identify the scale by objective quantitative measurement, skin surface measurements from the Visioscan~ VC98 were used. To test the reliability and validity of our wrinkle scale, a multi-rater consensus method was used. A double-blind, randomized, vehicle-controlled 12-week study was conducted to use this clinical photo-score to evaluate the efficacy and safety of Centella triterpenes cream~ in treating crow＇s feet. A newly developed 10-point photographic and descriptive scale emerged from this study. The final atlas of these photographs contained a total of 6 sets with 10 pictures each. From 0 to 9, surface evaluation of smoothness （SEsm） parametric measurements decreased progressively, indicating that the scale increased inversely. Weighted kappa coefficients for intra-assessor were between 0.75-0.87. The overall Kendall＇s coefficient is 0.86 on the first rating and 0.87 on the second rating. Thirty- six volunteers were recruited and 35 subjects completed a 12-week trial. Clinical photo-score by investigator showed a significant difference （P 〈 0.05） between the treatment side and control side after 4 weeks. Use of these scales in clinical settings to evaluate facial wrinkles in Asians individuals is recommended.

The Genus Carissa:An Ethnopharmacological,Phytochemical and Pharmacological Review

Carissa L.is a genus of the family Apocynaceae,with about 36 species as evergreen shrubs or small trees native to tropical and subtropical regions of Africa,Asia and Oceania.Most of Carissa plants have been employed and utilized in traditional medicine for various ailments,such as headache,chest complains,rheumatism,oedema,gonorrhoea,syphilis,rabies.So far,only nine Carissa species have been phytochemically studied,which led to the identification of 123 compounds including terpenes,flavonoids,lignans,sterols,simple phenolic compounds,fatty acids and esters,and so on.Pharmacological studies on Carissa species have also indicated various bioactive potentials.This review covers the peer-reviewed articles between 1954 and 2016,retrieved from Pubmed,ScienceDirect,SciFmder,Wikipedia and Baidu,using“Carissa”as search term(“all fields”)and with no specific time frame set for search.Fifteen important medicinal or ornamental Carissa species were selected and summarized on their botanical characteristics,geographical distribution,traditional uses,phytochemistry,and pharmacological activities.

Research Status of Chinese Medicinal Herbs Zexie (Rhizoma Alismatis) and Its Enlightenment to TCM Development in Guangxi

In this paper,the scientific research status of Zexie(Rhizoma Alismatis)was comprehensively expounded from the aspects of plant characteristics,source,chemical composition,pharmacological research and quality control methods,etc.The market situation of Rhizoma Alismatis was systematically analyzed from historical and current perspectives;aiming at the problems of poor quality and irregular processing of Chinese medicinal herbs Rhizoma Alismatis,some ideas were put forward to improve the quality and market value of medicinal materials of Rhizoma Alismatis,so as to make the Chinese herbal medicine industry develop towards a healthy and efficient direction.

UPLC-QTOF-MS Analysis of Extracts from the Leaves of <i>Pouteria caimito</i>(Sapotaceae) and Their Antioxidant Activity

This study describes the phytochemical profile and antioxidant activity of an extract from the leaves of Pouteria caimito (Sapotaceae). The extract in ethanol was obtained by maceration at room temperature and subjected to the liquid-liquid partition to obtain fractions in hexane and ethyl acetate. Steroids, triterpenes, saponins, alkaloids and flavonoids were identified by the phytochemical prospection of extracts and fractions from the leaves. The analysis of the ethyl acetate fraction by UPLC-QTOF-MS allowed us to identify eight triterpenes, namely, euscaphic acid (1), hyptadienic acid (2), betulinic acid (3), oleanolic acid (4), ursolic acid (5), 3β-(O-p-coumaroyl)- alphitolic acid (6), 3β-(O-p-coumaroyl)-maslinic acid (7) and 3β-(O-p-coumaroyl)-2-hydroxy-urs-12-en-28-oic acid (8). The ethanol extract and ethyl acetate fraction presented total phenolic contents of 10.6 ± 0.1 and 11.4 ± 0.3 mg GAE g-1, respectively, and considerable antioxidant activity in the DPPH assay with EC50 values of 299.4 ± 1.5 and 391.8 ± 0.9 μg·ml-1, respectively.