Immunomodulatory effects and structure-activity relationship of botanical pentacyclic triterpenes: A review / 中草药·英文版

Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as anti-oxidant, 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.

Pentacyclic triterpenes and other constituents in propolis extract from Melipona beecheii collected in Yucatan, México

ABSTRACT Thirteen pentacyclic triterpenes, methyl 3-oxours-12-en-23-oate, marsformosanone, taraxerone, β-amyrenone, α-amyrenone, lupenone, 24-methylencycloartan-3-one, moretenol acetate, β-amyrin acetate, germanicol acetate, 24-methylencycloartanyl acetate, β-amyrin, and α-amyrin were identified in a chloroform-methanol propolis extract from Melipona beecheii. Additionally, were identified in this propolis, hexadecanoic acid, methyl ester, octadecanoic acid, methyl ester and 1-triacontanol. The purification of the propolis extract was carried out using different chromatographic techniques, including vacuum liquid chromatography, gravity column chromatography and gel filtration chromatography Sephadex LH-20. The identification of the metabolites was performed using mass spectrometry.

Phytochemical compounds of anise hyssop (Agastache foeniculum) and antibacterial, antioxidant, and acetylcholinesterase inhibitory properties of its essential oil

Agastache foeniculum (Pursh) Kuntze (anise hyssop) is known as a medicinal and flavoring spice plant. The aim ofthis research was gas chromatography-mass spectrometry (GC-MS) analysis of anise hyssop essential oil and analysisof radical scavenging ability, antimicrobial activity, and acetylcholinesterase inhibitory activity. Phytochemicalcomposition of anise hyssop wastes and the aqueous extract obtained after steam distillation was investigated.Eight compounds were identified in essential oils by GC-MS analysis, as the major ones were phenylpropenoids[estragol—93.45% of total ion current (TIC), eugenol—0.15% of TIC, and methyl isoeugenol—2.48% of TIC]. Inthe anise hyssop wastes extract, four pentacyclic triterpenes were identified (betulin—36.1 mg/g, betulinic acid—2.4mg/g, oleanolic acid—160.0 mg/g, and ursolic acid—6.7 mg/g extract). Rosmarinic acid (50.6 mg/g extract) andflavonoids—myricetin (0.5 mg/g), luteolin (0.9 mg/g), and apigenin (0.6 mg/g) were detected by high-performanceliquid chromatography with diode-array detection analysis of aqueous extract. The anise hyssop essential oil showedstrong radical scavenging ability IC50—6.54 μl/ml. The results obtained from antimicrobial screening revealed thatessential oil possessed inhibitory activity against Staphylococcus aureus ATCC 25923, Curtobacterium flaccumfaciensPM_YT, Listeria monocytogenes, Bacillus subtilis ATCC 6633, Salmonella sp., Escherichia coli ATCC 8739, Proteusvulgaris, Pseudomonas aeruginosa ATCC 9027, Klebsiella pneumoniae, and Candida albicans, while Enterococcusfaecalis remained unaffected.

Research progress on natural pentacyclic triterpenoids and derivatives in anti-cardiovascular and cerebrovascular diseases / 中草药

Cardiovascular and cerebrovascular diseases are the leading cause of death among adult populations in China. The incidence and mortality rate shows an upward trend, and age of onset is younger trend. It is necessary to treat cardiovascular and cerebrovascular diseases with Chinese materia medica. Natural products have been the important and productive source of leading compounds for the development of anti-cardiovascular and cerebrovascular drugs. Naturally occurring triterpenoid saponins are generally plant-derived secondary metabolites with various valuable pharmacological properties. Pentacyclic triterpenoids of which show obvious anti-inflammatory, antitumor and antiviral effects. In recent years, increasing researches focused on the anticardiovascular and cerebrovascular mechanisms and modifications to improve the pharmacological activity and druggability of pentacyclic triterpenes. Based on previous studies, the literatures and patents of nearly 10 years on pentacyclic triterpenoids and their derivatives have been consulted. The research progress of anti-cardio-cerebrovascular activities of four types of compounds, oleanane, ursane, lupane, and friedelane, related to pentacyclic triterpenoids is reviewed, which provides a basis and reference for its further development and utilization in the treatment of cardiovascular and cerebrovascular diseases.

Antinociceptive and anti-inflammatory activities of a triterpene-rich fraction from Himatanthus drasticus

Himatanthus drasticus (Mart.) Plumel belongs to the Apocynaceae family and the latex from its trunk bark (Hd) is known as "janaguba milk". This latex is widely used in Northeast Brazil, mainly in the Cariri region, for its gastroprotective, anti-inflammatory, and antitumor properties. The objective of this study was to investigate a triterpene-rich fraction (FJNB) from H. drasticus latex on acute models of nociception and inflammation and to clarify its mechanisms of action. Wistar rats or Swiss mice were subjected to the carrageenan-induced paw edema test or the formalin test, respectively, after the acute oral treatment with FJNB. The inflamed paws from the carrageenan-induced paw edema and formalin tests were processed for histological and immunohistochemical assays, respectively. The results were analyzed by ANOVA and considered significant at P<0.05. FJNB (10 mg/kg) decreased the paw edema by 25% at the 3rd h after the carrageenan injection. Indomethacin, used as reference, inhibited the paw edema by 59% at the same time-point. In the formalin test, FJNB inhibited the 1st phase by 27, 49, and 52% and the 2nd phase by 37, 50, and 67%, at the doses of 1, 5, and 10 mg/kg, respectively. In addition, FJNB significantly inhibited the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha. The histone deacetylase (HDAC) expression and the transcription factor nuclear factor kappa (NF-kB) were also inhibited at the same doses. In conclusion, the FJNB inhibitory actions on iNOS, COX-2, TNF-α, HDAC, and NF-kB could be involved with the drug anti-inflammatory activity.

Maytenus distichophylla and Salacia crassifolia: source of products with potential acetylcholinesterase inhibition

ABSTRACT The phytochemical study of the extract leaves from Maytenus distichophylla Mart. and Salacia crassifolia (Mart. ex Schult.) G. Don, Celastraceae, resulted in the isolation of 3-oxofriedelane, 3β-hydroxyfriedelane, 3β,24-dihydroxyfriedelane, 3-oxo-28,29-dihydroxyfriedelane, two mixtures of pentacyclic triterpenes (α-amyrin with β-amyrin and 3β-stearyloxy-urs-12-ene with 3β-stearyloxy-olean-12-ene), 3β-palmityloxy-urs-12-ene, the steroid β-sitosterol and its glycosylated derivative β-glucosyl-β-sitosterol, tritriacontanoic acid and the natural polymer gutta percha. The chemical structures of these constituents were established by IR, 1H and 13C NMR spectral data. Crude extracts, the mixtures of triterpenes and the isolated constituents were subjected to in vitro acetylcholinesterase inhibitory evaluation. Acetylcholinesterase inhibitory effect was observed for crude chloroform extract leaves from M. distichophylla (100%) and S. crassifolia (97.93 ± 5.63%) and for the triterpenes 3β,24-dihydroxyfriedelane (99.05 ± 1.12%), 3-oxo-28,29-dihydroxyfriedelane (90.59 ± 3.76%) and 3β-palmityloxy-urs-12-ene (97.93 ± 1.47%). The percent inhibitions induced by these natural products were very similar to those produced by physostigmine (93.94 ± 2.10%) a standard acetylcholinesterase inhibitor. Therefore, these results open perspectives for the use of these species as source of compounds with similar physostigmine pharmacological effect.

Biological Activities and Stability of a Standardized Pentacyclic Triterpene Enriched Centella asiatica Extract

Pentacyclic triterpenes, mainly, asiatic acid, madecassic acid, asiaticoside, and madecassoside are the active constituents of Centella asiatica. A pentacyclic triterpene enriched C. asiatica extract (PRE) was prepared and standardized to contain a total pentacyclic triterpenes not less than 65% w/w. This work was focused on determination of antiinflammatory, antioxidant, and tyrosinase inhibitory activities of PRE and its stability. The PRE exhibited a satisfactory nitric oxide inhibitory effect, with an IC50 value of 64.6 µg/mL. In addition, the PRE inhibited tyrosinase enzyme activity with an IC50 value of 104.8 µg/mL. In contrast, the PRE possessed only weak antioxidant activity. The PRE was stable over a period of four months when stored as a dried powder but only in a well-closed container protected from light at 4 °C. An aqueous alcoholic solution of the PRE was stable at pH values of 5.8 and 7.0, but was not stable at a pH of 8.2. Preparations of the PRE in an aqueous solution should be performed in acidic or neutral conditions.

Chemical constituents of Sabia parviflora / 中草药

Objective: To investigate the chemical constituents from the stems and leaves of Sabia parviflora. Methods: Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, MCI, and semi-preparative HPLC were used repeatedly for separation and purification of chemical constituents, and their structures were identified by NMR and MS spectra data with those reported in literature. Results: Fourteen compounds were obtained from the petroleum ether extract of S. parviflora, and identified as β-sitosterol (1), mominine (2), (20S)-3-oxo-20-hydroxytaraxastane (3), fluoren-9-one (4), N-formyldehydroanonain (5), betulinic acid (6), dehydroformouregine (7), palmitic acid (8), 20-hydroxy-lupan-3-one (9), 3-oxooleanolic acid (10), erythrodiol (11), methyl betulinate (12), N-formyl-annonain (Z) (13), and N-formyl-O-methylisopiline (14). Conclusion: Among the 14 compounds, there are seven pentacyclic triterpenes, four alkaloids, and three other compounds; compounds 3-10 and 12-14 are isolated from this plant and the plants of Sabia Colebr. for the first time, and the 13C-NMR spectral assignments of compounds 5, 7, and 14 are reported for the first time.

Effect of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion in mice / 中华麻醉学杂志

Objective To evaluate the effects of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion (I/R) in mice.Methods Seventy-two male Kunming mice,aged 3 months,weighing 25-35 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (group S),I/R group,and betulinic acid preconditioning group (group BP).Cerebral I/R was induced by middle cerebral artery occlusion in mice anesthetized with 10％ chloral hydrate 40 ml/kg.In group BP,betulinic acid 50 mg/kg was administered by intragastric gavage everyday for 7 days before ischemia,while the equal volume of solvent dimethyl sulfoxide was given in S and I/R groups.At 22 h of reperfusion,neurological function was assessed and scored.The mice were then sacrificed and brains were removed for determination of infarct size,expression of NADPH oxidase (Nox1,Nox2 and Nox4) and p22phox mRNA,activity of ROS and apoptosis rate in the infarcted zone.Results Compared with S group,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly increased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was up-regulated in group I/R.Compared with group I/R,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly decreased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was down-regulated in group BP.Conclusion Betulinic acid preconditioning mitigates cerebral I/R injury through inhibiting oxidative stress response in mice.

Efecto in vitro de los terpenos lupeol y casearina G sobre células sanguíneas y tumorales / In vitro effect of lupeol and casearin G on peripheral blood mononuclear and tumor cells

Background: The rainforest is an important source of natural compounds with therapeutic properties. Although there are many anti-inflammatory and antineoplastic drugs available to the clinician, there is an ongoing need for new therapeutic drugs with fewer serious adverse effects. Aim: To evaluate the in vitro cytotoxic effects of lupeol and casearin G on tumor cells, on phagocytic activity and nitric oxide (NO) production by blood mononuclear cells. Material and Methods: The cytotoxic effect of these compounds on cell lines MCF-7 (human breast adenocarcinoma) and PC-3 (human prostate cancer) was measured by a colorimetric assay (MTS/PMS) and the sulphorhodamine B assay. Peripheral blood mononuclear cells were obtained from eight healthy volunteers. The effect of these compounds on nitric oxide (NO) production was measured using the Griess reaction. Their effect on phagocytic activity of PBMC was also evaluated. Results: Lupeol (≥ 2 mM) resulted in a reduction of both the phagocytic index and the percentage of phagocytic monocytes and macrophages. Treatment of monocytes/macrophages with lupeol (72 µM) and casearin G (4 µM) reduced the production of NO. Neither lupeol (< 969 µM) nor casearin G (< 55 µM) had cytotoxic effects on PBMC. Casearin G showed both cytotoxic (IC50, LC50) and cytostatic (GI50) effects against tumor cells, PC-3 (IC50 = 12.5 µM; GI50 = 13.3 µM; LC50 = 51.9 µM) and MCF-7 (IC50 = 112.8 µM; GI50 = 11.8 µM; LC50 = 49.4 µM), as well as a hemolytic effect (≥ 182 µM). Conclusions: These observations indicate that lupeol and casearin G might be useful compounds in the preparation of anti-inflammatory drugs, whereas casearin G might be useful in the elaboration of antitumor drugs.

Maytenus salicifolia Reissek, Celastraceae: triterpenes isolated from stems and antioxidant property of extracts from aerial parts

Six pentacyclic triterpenes were isolated from hexane extract of stems of Maytenus salicifolia Reissek, Celastraceae: 30-hydroxyfriedelan-3-one (1), 3,16-dioxofriedelane (2), friedeline (3), lupeol (4), betuline (5) and lup-20(29)-en-3,30-diol (6). The structure each one was established on the basis of detailed ¹H and 13C NMR spectral investigation and by comparison with the respective literature values. For compound 1, the complete 2D NMR (HMBC, HMQC and NOESY) spectral data were herein reported for the first time. Compounds 1, 2, 5 and 6 were isolated for the first time from this plant. Antioxidant activity is described for some extracts from species of the Celastraceae family, then, the extracts from aerial parts of M. salicifolia were evaluated in relation to antioxidant potential using the DPPH method. Compared to quecertin, the AcEt extract (EAF) from leaves, AcEt (EAPF) and MeOH (EMPF) from pulp fruit and AcEt (EAT) and MeOH (EMT) from stems showed significant antioxidant property.

Chemical constituents from the stem of Brosimum potabile (Moraceae) / Constituintes químicos do cerne de Brosimum potabile (Moraceae)

Three coumarins, 5-methoxypsoralene, xanthyletin, and (-)-marmesin, have been isolated from the ethanolic extract of the stem of the Amazonian plant Brosimum potabile. The structures were determined on the basis of NMR analyses and by comparison with spectroscopic data in the literature. The analysis of the hexane fractions by GC-MS in EIMS mode suggested the presence of (1-methylpentyl)-benzene; α,α-dimethyl-4-(1-methylethyl)-benzenemethanol; 1-methyl-3,5-bis(1-methylethyl)-benzene; urs-12-ene; chola-5,22-dien-3ß-ol; cholesta-4,6-dien-3ß-ol; sitosteryl 9(Z)-octadecenoate; cholesta-5,22-dien-3ß-ol; cholesta-4,6,22-trien-3-one; and cholesta-4,22-dien-3-one. NMR data of other hexane fractions indicated the presence of 3ß-acetoxy-lup-12,20(29)-diene; 3ß-acetoxy-olean-12-ene; 3ß-acetoxy-urs-12-ene; and adian-5-ene. All these compounds are first described in B. potabile.

Três cumarinas, 5-metoxipsoraleno, xantiletina e (-)-marmesina, foram isoladas no extrato etanólico do cerne da planta amazônica Brosimum potabile. Suas estruturas foram determinadas a partir das análises por RMN e por comparação com dados espectroscópicos da literatura. As análises das frações hexânicas por CG/EM sugeriram a presença de (1-metilpentil)-benzeno; α,α-dimetil-4-(1-metiletil)-benzenometanol; 1-metil-3,5-bis(1-metiletil)-benzeno; urs-12-eno; cola-5,22-dien-3ß-ol; colesta-4,6-dien-3ß-ol; (9Z)-octadecenoato de sitosterila; colesta-5,22-dien-3ß-ol; colesta-4,6,22-trien-3-ona e colesta-4,22-dien-3-ona. Dados de RMN de outras frações hexânicas indicaram a presença de 3ß-acetóxi-lup-12,20(29)-dieno; 3ß-acetóxi-olean-12-eno; 3ß-acetóxi-urs-12-eno e adian-5-eno. Todos esses compostos foram identificados pela primeira vez em B. potabile.

Four Brazilian Maytenus salicifolia Reissek (Celastraceae) groups studied by TLC and UV/Vis spectrophotometry / Estudo de quatro populações de Maytenus salicifolia Reissek (Celastraceae) por CCD e espectrometria na região do UV/Vis

The great variety of angiosperms shows the need to development of botanical classification systems supported by phytochemistry, biochemistry and others. Recently, techniques of analysis used for the isolation and characterization of secondary metabolites have been employed as auxiliary quick and efficient methods for the identification and classification of plant species. M. salicifolia is popularly known in Brazil, as "small coffee" and decoct obtained from its fresh leaves is topically used to alleviate itches and other skins allergic symptoms. This work presents the use of TLC and UV/Vis spectrophotomety processes to be applied like an auxiliary method in botanical taxonomy. The results demonstrate that this process can be used in differentiation of the same genera species, and in the selection of chemical variations between individuals of the same species.

A grande variedade de angiospermas apontou a necessidade do desenvolvimento de sistemas de classificação botânica apoiada pela fitoquímica, bioquímica e outras. Recentemente, técnicas de análise utilizadas para o isolamento e caracterização de metabólitos secundários vêm sendo empregadas como métodos auxiliares rápidos e eficientes para identificação e classificação de espécies vegetais. M. salicifolia é popularmente conhecida no Brasil, como "cafezinho". O chá obtido a partir de folhas frescas é usado topicamente para aliviar pruridos e sintomas alergiformes. Este trabalho apresenta a utilização do CCD em sílica gel e espectrofotometria no UV / Vis como métodos auxiliares na identificação botânica de M. salicifolia. Os resultados demonstraram que este processo pode ser usado na diferenciação de plantas do mesmo gênero, assim como detectar variações químicas entre indivíduos de uma mesma espécie.

Evaluation of antibacterial activity of "Mangabarana" Austroplenckia populnea Reissek (Celastraceae) / Avaliação da atividade antibacteriana de "Mangabarana" Austroplenckia populnea Reissek (Celastraceae)

Austroplenckia populnea (Mangabarana) is popularly used by people from Minas Gerais, Brazil for dysenteries diseases treatment. Antitumor and antiulcer activities were also attributed to this plant. Extracts obtained using solvents of different polarities and pentacyclic triterpenes (PCTTs) isolated from these extracts through phytochemical methods were submitted to antibacterial assays. The results showed the existence of this activity and open perspectives for news studies with other organic compounds isolated from this plant.

Austroplenckia populnea (Mangabarana) é popularmente utilizada em Minas Gerais, Brasil, para o tratamento de disenterias. A ela também são atribuídas propriedades antitumoral e antiúlcera. Extratos de partes desta planta obtidos com solventes de diferentes polaridades e triterpenos pentacíclicos (TTPCs) isolados destes, por métodos fitoquímicos foram submetidos a testes de atividade antibacteriana. Os resultados mostraram a existência desta atividade e abriram perspectivas para a continuidade dos estudos com outros compostos orgânicos isolados desta planta.