Oleanane Derivatives Research Articles

Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids

For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC50 1.0–9.0 μM in the tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition test. Lupane derivatives – 1-oxime 7, 1,10-seco-hydroxynitrile 11 and furanoterpenoid 14 – were selected as those expected to be the most promising compounds. The results of molecular modeling evinced the strongest binding of compound 11 to the active site of Tdp1 compared to the reference drug. Simultaneously, only compound 11 at subtoxic concentration (10 μM) produced a synergetic effect on the topotecan activity against HeLa-V cells.

Stereoselective Epoxidation of Triterpenic Allylic Alcohols and Cytotoxicity Evaluation of Synthesized Compounds.

The epoxidation process of semi-synthetic triterpenoids 2-methyl-3-oxo-19β,28-epoxy- 18α-olean-1-ene, and its allylic alcohol derivatives were examined. 1,2α-epoxide, as the main product, was found to be formed from the starting enone exposed to m-chloroperbenzoic acid (mCPBA). In the case of hydroxy-directed mCPBA-oxidation of triterpenic allyl alcohols and their 3α-alkyl-substituted derivatives, inversion of C1 and C2 asymmetric centers with the formation of 1,2β-epoxyalcohols took place. The synthesis of 2,3α-epoxides was fulfilled from 2,3-dialkyl-substituted C(3) allyl alcohols by the action of pyridinium chlorochromate under [1,3]-oxidative rearrangement conditions. The transformations brought about enabled chiral oleanane derivatives with an oxygen-containing substituent at the C1, C2, and C3 atoms to be obtained. The study also provides information on in silico PASS prediction of pharmacological effects and in vitro evaluation of the cytotoxic activity of the synthesized compounds.

An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets

The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. Communicated by Ramaswamy H. Sarma

Phytochemistry and biological activities of Polemonium caeruleum L.

Polemonium caeruleum L. is a Chinese medicinal plant used in the treatment of tuberculosis, whooping cough, fever, infertility, epilepsy, endometritis and insomnia. It was also used as sedative and anaesthetic agent. In this work the phytochemical investigation using LC-ESI-QTOF-MS and GC–MS techniques was done for chemical characterization of methanol extracts of underground and aerial plant parts. In the course of our studies on medicinal plants, we evaluated the extracts of P. caeruleum for their biological activities as antimicrobial, antimalarial, anti-leishmanial and antitrypanosomal agents and we investigated their cytotoxicity towards mammalian cells – HEK293 and Vero cell lines, both originating from kidney and also against pharyngeal squamous cell carcinoma, FaDu cell line. LC-ESI-QTOF-MS analysis confirmed the presence of triterpene saponins – oleanane derivatives (polemoniumsaponins, glycosides of theasapogenol derivatives and β-amyrin among others), as well as flavonoid glycosides with most predominant acacetin derivatives. Saponins were more abundant and varied in the extract from underground parts of the plant, while flavonoids dominated in the extract from aerial parts. GC–MS performed after silanization enabled the identification of carbohydrates, fatty acid esters, amino acids and carboxylic acids. In the present study, the antibacterial activity of crude extract of the aerial parts of P. caeruleum against Escherichia coli with an IC50 of 137.0 μg/mL and antitrypanosomal activity of crude extract of the underground parts of P. caeruleum with an IC50 of 16.03 μg/mL were reported. The cytotoxicity of the extract from underground parts of P. caeruleum was in a range 44.5–63.5 μg/ml, while cytotoxicity of the extract from aerial parts ranged from 93.8 to 178.0 μg/ml.

Two new oleanane derivatives from the fruits of Leonurus japonicus and their cytotoxic activities.

Two new oleanane derivatives, leonuronins A and B (1 and 2), along with three known oleanane triterpenes (3-5) were isolated from the fruits of Leonurus japonicus. Their structures were elucidated on the basis of NMR, MS, IR and UV spectroscopic data. The new compounds were tested for cytotoxic activities against A549 and Hela cancer cell lines. Compounds 1 and 2 exhibited weak cytotoxicity with IC50 values ranging from 6.97 to 18.13μM.

New Triterpenoids from the Leaves of Alafia barteri

A new oleanane derivative, 3β-acetyloleana-5,12-dien-2,23-diol (1), and a new lupane compound, lup-11,20(29)-dien-3 β,28-diol (2), together with eight known compounds, oleana-5,12-dien-3β-yl acetate (3), lup-5,20(29)-dien-3 β -yl acetate (4), 18-methylethylnonadecan-19-oic-9-enoate (6), octadecane (5), cis-pentadec-7-enoic acid (7), cis-tetradec-7,10-dienoic acid (8), cholest-4-en-3-one (9), and stigmasterol (10), were isolated from the leaves of Alafia barteri. Their structures were elucidated by IR, 1D and 2D NMR, and mass spectroscopy. Compounds 7 and 8 exhibited cytotoxic activities against K562, WRL, and MCF-7 tumor cell lines with IC50 in the range of 8.80 to 37.10 μg/mL, while compounds 2 and 9 suppressed the viability of K562 cells with IC50 of 120.2 and 14.48 μg/mL. Compounds 1, 3, and 4 showed low cytotoxic properties on the tested cell lines.

Synthesis of cytotoxically active derivatives based on alkylated 2,3-seco-triterpenoids

Extremely low content of biologically active triterpenoids with the fragmented or contracted ring A extractable from plants is the main disadvantage of their use in drug discovery and practical pharmacology. Development of new methods for synthesis of these compounds and their structural analogs from bioavailable triterpene precursors gives an opportunity to obtain promising agents for pharmacology with excellent yields. A new approach to synthesis of alkylated A-seco-triterpenoids, including the Beckmann fragmentation of 3-methyl-substituted allobetulin or betulinic acid methyl ester with 2-hydroxyimino group in the ring A was proposed. These compounds were used to prepare a series of 2,3-seco- and five-membered ring A lupane and oleanane derivatives, cytotoxicity of which was screened in vitro against the cancer (HEp-2, HCT 116, A549, RD TE32, MS) and non-cancerous (HEK 293) cell lines. Methyl 3-bromomethyl-1-cyano-3-oxo-2,3-seco-2-norlup-20(29)-en-30-al-28-oate was selected as the most active compound (IC50 3.4–10.4 μM for HEp-2, HCT 116, RD TE32, MS cells) capable of triggering caspase-8-mediated apoptosis in HCT 116 cells accompanied by typical apoptotic chromatin condensation, without any loss of mitochondrial membrane permeability.

Oleanane-type glycosides from Pittosporum tenuifolium “variegatum” and P. tenuifolium “gold star”

The phytochemical study of two cultivars of Pittosporum tenuifolium Banks & Sol. ex Gaertn, “variegatum” and “gold star”, led to the isolation of eight oleanane-type glycosides: seven previously undescribed and a known one. Their aglycons are oxygenated oleanane derivatives as barringtogenol C, camelliagenin A, hederagenin, and 22α-hydroxyoleanolic acid. Their structures were established by 2D NMR spectroscopic techniques and mass spectrometry as 3-O-β-D-galactopyranosyl-(1 → 2)-[α-L-arabinopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-21-O-angeloyl-22-O-acetylbarringtogenol C, 3-O-β-D-galactopyranosyl-(1 → 2)-[α-L-arabinopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-21,22-di-O-angeloylbarringtogenol C, 3-O-β-D-galactopyranosyl-(1 → 2)-[α-L-arabinopyranosyl-(1 → 3)]-β-D-glucuronopyranosyl-22-O-angeloylcamelliagenin A, 3-O-β-D-glucopyranosyl-(1 → 2)-[β-D-glucopyranosyl-(1 → 6)]-β-D-glucopyranosyl-22-O-[(6-O-acetyl)-β-D-glucopyranosyl]camelliagenin A, 3-O-β-D-galactopyranosyl-(1 → 2)-[α-L-arabinofuranosyl-(1 → 4)]-β-D-glucuronopyranosylhederagenin 28-O-β-D-glucopyranosyl ester, 3-O-α-L-arabinofuranosyl-(1 → 4)-β-D-glucuronopyranosylhederagenin 28-O-β-D-glucopyranosyl ester, 3-O-β-D-galactopyranosyl-(1 → 2)-[α-L-arabinofuranosyl-(1 → 4)]-β-D-glucuronopyranosyl-22α-hydroxyoleanolic acid 28-O-β-D-glucopyranosyl ester, and the known ilexoside XLIX. These results represent a significative contribution to the chemotaxonomy of the genus Pittosporum, highlighting hederagenin-type saponins as chemotaxonomic markers of P. tenuifolium cultivars.

Vascular Endothelium-Dependent and Independent Actions of Oleanolic Acid and Its Synthetic Oleanane Derivatives as Possible Mechanisms for Hypotensive Effects.

PurposePlant-derived oleanolic acid (OA) and its related synthetic derivatives (Br-OA and Me-OA) possess antihypertensive effects in experimental animals. The present study investigated possible underlying mechanisms in rat isolated single ventricular myocytes and in vascular smooth muscles superfused at 37°C.MethodsCell shortening was assessed at 1 Hz using a video-based edge-detection system and the L-type Ca2+ current (ICaL) was measured using the whole-cell patch-clamp technique in single ventricular myocytes. Isometric tension was measured using force transducer in isolated aortic rings and in mesenteric arteries. Vascular effects were measured in endothelium-intact and denuded vessels in the presence of various enzyme or channel inhibitors.ResultsOA and its derivatives increased cell shortening in cardiomyocytes isolated from normotensive rats but had no effect in those isolated from hypertensive animals. These triterpenes also caused relaxation in aortic rings and in mesenteric arteries pre-contracted with either phenylephrine or KCl-enriched solution. The relaxation was only partially inhibited by endothelium denudation, and also partly inhibited by the cyclooxygenase (COX) inhibitor indomethacin, with no additional inhibitory effect of the NO synthase inhibitor, N-ω-Nitro-L-arginine. A combination of both ATP-dependent channel inhibition by glibenclaminde and voltage-dependent K+ channel inhibition by 4-aminopyridine was necessary to fully inhibit the relaxation.ConclusionThese data indicate that the effects of OA and its derivatives are mediated via both endothelium-dependent and independent mechanisms suggesting the involvement of COX in the endothelium-dependent effects and of vascular muscle K+ channels in the endothelium-independent effects. Finally, our results support the view that the antihypertensive action of OA and its derivatives is due to a decrease of vascular resistance with no negative inotropic effect on the heart.

Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals.

PurposeThe triterpene oleanolic acid (OA) is known to possess antihypertensive actions. In the present study we to compared the effects of the triterpene on mean arterial blood pressure (MAP) and kidney function following acute administration in normotensive animals with those of its related oleanane synthetic derivatives (brominated oleanolic acid, Br-OA and oleanolic acid methyl ester, Me-OA). We also used experimental models of hypertension to further explore the effects of sub-chronic oral OA treatment and evaluated influences on oxidative status.MethodsOA was extracted from dried flower buds of Syzygium aromaticum using a previously validated protocol in our laboratory. Me-OA and Br-OA were synthesized according to a method described. Rats were supplemented with lithium chloride (12 mmol L-1) prior to experimentation in order to raise plasma lithium to allow measurements of lithium clearance and fractional excretion (FELi) as indices of proximal tubular Na+ handling. Anaesthetized animals were continuously infused via the right jugular with 0.077M NaCl. MAP was measured via a cannula inserted in the carotid artery, and urine was collected through a cannula inserted in the bladder. After a 3.5 h equilibration, MAP, urine flow, electrolyte excretion rates were determined for 4 h of 1 h control, 1.5 h treatment and 1.5 h recovery periods. OA, Me-OA and Br-OA were added to the infusate during the treatment period. We evaluated sub-chronic effects on MAP and kidney function in normotensive Wistar rats and in two animal models of hypertension, spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (DSS) rats, during 9-week administration of OA (p.o.). Tissue oxidative status was examined in these animals at the end of the study. Increasing evidence suggests that and renal function disturbances and oxidative stress play major roles in the pathogenesis of hypertension.ResultsAcute infusion OA and oleanane derivatives displayed qualitatively similar effects in decreasing MAP and increasing urinary Na+ outputs. The drugs increased the FENa and FELi without influencing GFR indicating that at least part of the overall natriuretic effect involved proximal tubular Na+ reabsorption. Sub-chronic OA administration (p.o.) also elicited hypotensive responses in Wistar, DSS and SHR rats. The MAP lowering effect was more marked in hypertensive animals and were positively correlated with increased urinary Na+ excretion. Compared with respective control rats, OA treatment reduced malondialdehyde (MDA, a marker of lipid peroxidation) and increased activities of antioxidant enzymes; superoxide dismutase and glutathione peroxidase in hepatic, cardiac and renal tissues.ConclusionsOA and oleanane derivatives have similar effects on MAP, kidney function and oxidative stress. The amelioration of oxidative stress and blood pressure lowering effects by OA are more marked in hypertensive animals and correlated with an increased urinary Na+ output.Novelty of the WorkThe results of this study are novel in that they show 1) a correlation between blood pressure reduction and increased urinary Na+ excretion by OA, 2) a more marked MAP reduction in hypertensive animals and 3) a drug-induced decrease in proximal tubule Na+ reabsorption. The results may also be clinically relevant because OA is effective via oral administration.

Whole‐cell biotransformation of oleanolic acid by free and immobilized cells of Nocardia iowensis: Characterization of new metabolites

In this study, Nocardia iowensis was used to transform oleanolic acid (OA) into oleanane derivatives. The first derivative, which was found after 24 h of cultivation, was the known and already described OA methyl ester. After 1 week, two other derivatives (oleanonic acid methyl ester and an unknown metabolite) were identified as new products of a biotransformation by N. iowensis. These oleanane metabolites were characterized by HPLC, HPLC‐ESI‐MS, and HPLC‐1H NMR spectroscopy. The biotransformation was performed by suspended and immobilized cells (ICs) of N. iowensis. Cells immobilized in alginate beads were used in order to prepare a continuous process. The substrate uptake of free and ICs was similar, whereas the peak area of OA methyl ester of the ICs was only about 10% of the native cells. However, the final product (oleanonic acid methyl ester) concentrations were similar in both approaches, whereas the unknown metabolite 3 was only detected transiently in the medium of ICs. Based on these results, a new biosynthetic pathway for the biotechnological production of oleanonic acid methyl ester is proposed.

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives.

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.

Lupane, friedelane, oleanane, and ursane triterpenes from the stem of Siphonodon celastrineus Griff

Twenty-one triterpenes consisting of a lupane derivative, two friedelanes, an oleanane derivative, and 17 ursane-type triterpenoids, together with three known triterpenes, three sterols, a fatty acid, a sesquiterpene alkaloid, and a glycerol derivative, were isolated from the stem of Siphonodon celastrineus. Their structures were characterized by various spectroscopic techniques, as well as comparison with literature data. Twenty-seven metabolites of these were evaluated for cytotoxic activity against six human cancer cell lines. The biosynthetic formation of a 1,4-dioxane bridge is also discussed.

Triterpene Saponins from the Aerial Parts of Trifolium medium L. var.sarosiense

Seven previously unreported triterpene glycosides (1-7) were isolated from methanol extract of the aerial parts of Trifolium medium var. sarosiense (zigzag clover). Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS and HRMS analyses. Compounds 1-7 are oleanane derivatives characterized by the presence of a keto group at C-22 of an aglycone and a primary alcoholic function at C-24 and differing functions at C-30. Among these, compounds 1-3 and 6 showed a secondary alcoholic function at C-11, which is methoxylated in compounds 4 and 7. Compound 5 was shown to possess a known aglycone, wistariasapogenol A; however, it is described here for the first time as a saponin constituent of the Trifolium genus. Some aspects of taxonomic classification of zigzag clover are also discussed.

Synthesis and Biological Evaluation of Novel Pyrazolo[4,3‐b]oleanane Derivatives as Inhibitors of Glycogen Phosphorylase

Eighteen pyrazolo[4,3-b]oleanane derivatives have been synthesized and biologically evaluated as inhibitors of rabbit muscle GPa. Key compound 5 was readily obtained in four steps starting from oleanolic acid (OA; 1). Further modification based on pyrazolo triterpene 5 resulted in 17 novel pyrazolo pentacyclic triterpenes. All of the synthesized pyrazolo[4,3-b]oleanane derivatives were biologically assayed against rabbit muscle GPa. Within this series of compounds, pyrazole triterpene 19 (IC(50)=9.9 microM) exhibited more potent activity than the parent compound 1. Preliminary structure-activity relationship analysis of the pyrazolo[4,3-b]oleanane derivatives as GPa inhibitors is discussed.

Oleanane Saponins from Stylosanthes erecta

Five new oleanane saponins (1-5) together with four know flavonol glycosides were isolated from the aerial parts of Stylosanthes erecta. Their structures were elucidated by 1D and 2D NMR experiments including 1D-TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The aglycone moieties of 1-4 were assigned as new oleanane derivatives.

ANTIVIRAL EFFECTS OF SAIKOSAPONINS ON HUMAN CORONAVIRUS 229E IN VITRO

SUMMARY 1Saikosaponins represent a group of oleanane derivatives, usually as glucosides, that are found in a number of plant families. Saikosaponins isolated from medicinal plants such as Bupleurum spp., Heteromorpha spp. and Scrophularia scorodonia have been reported to possess various biological activities, specifically antihepatitis, antinephritis, antihepatoma, anti‐inflammation, immunomodulation and antibacterial effects.2The aim of the present study was to examine the anticoronaviral activity of saikosaponins (A, B2, C and D) and their mode of action. Using the 2,3‐bis[2‐methoxy‐4‐nitro‐5‐sulfophenyl]‐5‐[(phenylamino) carbonyl‐2H‐tetrazolium hydroxide] (XTT) assay, results showed that all saikosaponins tested demonstrated antiviral activity at concentrations of 0.25–25 µmol/L, with the strongest activity being noted for saikosaponin B2 (IC50 = 1.7 ± 0.1 µmol/L). Interestingly, both saikosaponins A (50% cellular cytotoxicity (CC50) concentration = 228.1 ± 3.8 µmol/L; selectivity index (SI) = 26.6) and B2 (CC50 = 383.3 ± 0.2 µmol/L; SI = 221.9) exhibited no cytotoxic effects on target cells at concentrations that achieved antiviral activity. In the time‐of‐addition studies, saikosaponin B2, at 6 µmol/L, significantly inhibited human coronavirus 229E infection following its addition at various time pre‐infection (−4 to −1 h), coinfection (0 h) and post‐infection (1–4 h). Furthermore, saikosaponin B2 also showed an inhibitory effect on viral attachment and penetration.3The present results indicate that saikosaponin B2 has potent anticoronaviral activity and that its mode of action possibly involves interference in the early stage of viral replication, such as absorption and penetration of the virus.

Triterpenoid Saponins from Campsiandra guayanensis

Thirteen new triterpenoid saponins (1-13) were isolated from the aerial parts of Campsiandra guayanensis. Their structures were elucidated by 1D and 2D NMR experiments including 1D-TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The aglycon moieties of 1-10 were assigned as oleanane derivatives and those of 11-13 as lupane derivatives.

Preparation and Conformational Study of 19β,28-Epoxy-18α-olean-5-ene Derivatives

New oleanane type triterpenoids with the 5(6) double bond were prepared using partial demethylation on carbon C-4. The starting compound was 23-hydroxybetulin (1b) and the key reaction was the methylation of 19β,28-epoxy-24-nor-18α-olean-4-en-3-one (3b). The 5(6) double bond was used in preparation of new derivatives with an epoxy or oxo substituent in ring B. The conformation of ring A of new type 3-oxo oleanane derivatives with a double bond or a substituent on ring B was elucidated from vicinal coupling constants of hydrogen atoms in positions 1 and 2.

Effect of triterpenoids on the inflammation induced by protein kinase C activators, neuronally acting irritants and other agents

In order to establish the mode of the anti-inflammatory activity of triterpenoids, 11 naturally occurring compounds were assayed on mouse ear oedema induced by the protein kinase C activators, mezerein, 12- O-tetradecanoylphorbol-13-acetate (TPA), two 12-deoxyphorbol-13-monoesters (13-tetradecanoate (DPT) and 13-phenylacetate (DPP)) and bryostatin 1, and by resiniferatoxin, xylene and arachidonic acid. The effects on bradykinin-induced paw oedema and on the rat skin inflammation caused by hydrogen peroxide were also examined. The oedema induced by mezerein and DPT was reduced to different extents by the triterpenoids administered epicutaneously (0.5 mg per ear). Against DPT-induced oedema, lupane and oleanane derivatives were the most effective compounds. Oleananes and lupanes possessing a carboxyl group were active against bryostatin 1-induced oedema. Most of the triterpenoids were ineffective against the neurogenic inflammation caused by resiniferatoxin and xylene. Many triterpenoids, especially oleanane and lupane alcoholic derivatives, were active against the plantar oedema induced by bradykinin and on the intradermal inflammation induced by hydrogen peroxide. In conclusion, the anti-inflammatory activity of triterpenoids may depend on inhibition of protein kinase C, without any involvement of neurogenic inflammatory mechanisms.