Astraoleanosides E-P, oleanane-type triterpenoid saponins from the aerial parts of Astragalus membranaceus Bunge and their ß-glucuronidase inhibitory activity.

Historically, Astragalus membranaceus Bunge has been used as a beneficial medicinal plant, particularly in the Asian traditional medical systems, for the treatment of various human diseases such as stomach ulcers, diarrhea, and respiratory issues associated with phlegm. In this study, a phytochemical characterization of the aerial parts of A. membranaceusled to the isolation of 29 oleanane-type triterpenoid saponins, including 11 new compounds named astraoleanosides E-P (6-9, 13, 14, 18-22), as well as 18 known ones. The structures of these compounds were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. Among them, astraoleanoside H (9) and cloversaponin III (15) demonstrated the most potent ß-glucuronidase inhibitory activities, with IC50 values of 21.20 ± 0.75 and 9.05 ± 0.47 µM, respectively, compared to the positive control d-saccharic acid 1,4-lactone (IC50 = 20.62 ± 1.61 µM). Enzyme kinetics studies were then conducted to investigate the type of inhibition exhibited by these active compounds. In addition, the binding mechanism, key interactions, binding stability, and dynamic behavior of protein-ligand complexes were investigated through in silico approaches, such as molecular docking and molecular dynamics simulations. These findings highlight the promising potential of triterpenoid saponins from A. membranaceus as lead compounds for ß-glucuronidase inhibitors, offering new possibilities for the development of therapeutic agents targeting various diseases where ß-glucuronidase plays a crucial role.

Integrative transcriptome and single-cell sequencing technology analysis of the potential therapeutic benefits of oleanolic acid in liver injury and liver cancer.

BACKGROUND: Oleanolic acid has important hepatoprotective effects and inhibits liver tissue carcinogenesis. The aim of this study was to investigate the mechanism of action of oleanolic acid in inhibiting liver injury and liver cancer. METHOD: In this study, we applied differential gene analysis and gene enrichment analysis to identify the targets of oleanolic acid for the treatment of liver injury. And this study also applied Cibersort and GSVA methods to investigate the targets of oleanolic acid in liver injury. Based on oleanolic acid targets, we explored the major targets and further explored the role of the major targets in liver cancer. This study used the oncoPredict and the TIDE algorithm to predict the effect of oleanolic acid on drug resistance. Finally, the binding effect of oleanolic acid to relevant targets was explored using molecular docking techniques. RESULT: In this study, oleanolic acid was found to inhibit liver injury and promote liver regeneration mainly by promoting elevated expression of HMOX1. Oleanolic acid can inhibit oxidative stress and promotes Ferroptosis in liver injury. In liver cancer, we identified that the main target of oleanolic acid is HMOX1 and HDAC1. And we determined that HMOX1 promotes Ferroptosis in liver cancer. This reduced the sensitivity of liver cancer to targeted therapies and immunotherapy. Molecular docking showed high binding of oleanolic acid to HDAC1 and HMOX1. CONCLUSIONS: Oleanolic acid is an antioxidant by promoting high expression of HMOX1 and promotes the development of Ferroptosis in liver cancer and liver injury.

Foegraecumoside O and P, a Pair of Triterpenoid Saponins with a 4/5/6 Fused Tricyclic Oleanane Carbon Skeleton from Lysimachia foenum-graecum Hance.

Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC50 at 12.4-19.2 µM in an MTT assay, comparing with the positive control doxorubicin, which had IC50 at 0.53-4.92 µM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed.

Comparative genomics of the medicinal plants Lonicera macranthoides and L. japonica provides insight into genus genome evolution and hederagenin-based saponin biosynthesis.

Lonicera macranthoides (LM) and L. japonica (LJ) are medicinal plants widely used in treating viral diseases, such as COVID-19. Although the two species are morphologically similar, their secondary metabolite profiles are significantly different. Here, metabolomics analysis showed that LM contained ~86.01 mg/g hederagenin-based saponins, 2000-fold higher than LJ. To gain molecular insights into its secondary metabolite production, a chromosome-level genome of LM was constructed, comprising 9 pseudo-chromosomes with 40 097 protein-encoding genes. Genome evolution analysis showed that LM and LJ were diverged 1.30-2.27 million years ago (MYA). The two plant species experienced a common whole-genome duplication event that occurred ∼53.9-55.2 MYA before speciation. Genes involved in hederagenin-based saponin biosynthesis were arranged in clusters on the chromosomes of LM and they were more highly expressed in LM than in LJ. Among them, oleanolic acid synthase (OAS) and UDP-glycosyltransferase 73 (UGT73) families were much more highly expressed in LM than in LJ. Specifically, LmOAS1 was identified to effectively catalyse the C-28 oxidation of ß-Amyrin to form oleanolic acid, the precursor of hederagenin-based saponin. LmUGT73P1 was identified to catalyse cauloside A to produce α-hederin. We further identified the key amino acid residues of LmOAS1 and LmUGT73P1 for their enzymatic activities. Additionally, comparing with collinear genes in LJ, LmOAS1 and LmUGT73P1 had an interesting phenomenon of 'neighbourhood replication' in LM genome. Collectively, the genomic resource and candidate genes reported here set the foundation to fully reveal the genome evolution of the Lonicera genus and hederagenin-based saponin biosynthetic pathway.

Oleanolic Acid Glycosides from Scabiosa caucasica and Scabiosa ochroleuca: Structural Analysis and Cytotoxicity.

In the field of research on medicinal plants from the Armenian flora, the phytochemical study of two Scabiosa L. species, S. caucasica M. Bieb. and S. ochroleuca L. (Caprifoliaceae), has led to the isolation of five previously undescribed oleanolic acid glycosides from an aqueous-ethanolic extract of the roots: 3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid 28-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl ester, 3-O-ß-D-xylopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid 28-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl ester, 3-O-ß-D-xylopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid, 3-O-ß-D-xylopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)]-ß-D-xylopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid 28-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyloleanolic acid 28-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl ester. Their full structural elucidation required extensive 1D and 2D NMR experiments, as well as mass spectrometry analysis. For the biological activity of the bidesmosidic saponins and the monodesmosidic saponin, their cytotoxicity on a mouse colon cancer cell line (MC-38) was evaluated.

Recent advances in medicinal chemistry of oleanolic acid derivatives.

Oleanolic acid (OA), a ubiquitous pentacyclic oleanane-type triterpene isolated from edible and medicinal plants, exhibits a wide spectrum of pharmacological activities and tremendous therapeutic potential. However, the undesirable pharmacokinetic properties limit its application and development. Numerous researches on structural modifications of OA have been carried out to overcome this limitation and improve its pharmacokinetic and therapeutic properties. This review aims to compile and summarize the recent progresses in the medicinal chemistry of OA derivatives, especially on structure-activity relationship in the last few years (2010-2021). It gives insights into the rational design of bioactive derivatives from OA scaffold as promising therapeutic agents.

Selected plant triterpenoids and their amide derivatives in cancer treatment: A review.

Medicinal plants have been used to treat different diseases throughout the human history namely in traditional medicine. Most of the plants mentioned in this review article belong among them, including those that are widely spread in the nature, counted frequently to be food and nutrition plants and producing pharmacologically important secondary metabolites. Triterpenoids represent an important group of plant secondary metabolites displaying emerging pharmacological importance. This review article sheds light on four selected triterpenoids, oleanolic, ursolic, betulinic and platanic acid, and on their amide derivatives as important natural or semisynthetic agents in cancer treatment, and, in part, in pathogenic microbe treatment. A literature search was made in the Web of Science for the given key words covering the required area of secondary plant metabolites and their amide derivatives. The most recently published findings on the biological activity of the selected triterpenoids, and on the structures and biological activity of their relevant amide derivatives have been summarized therein. Mainly anti-cancer effects, and, in part, antimicrobial and other effects of the four selected triterpenoids and their amide derivatives have also been reviewed. A comparison of the effects of the parent plant products and those of their amide derivatives has been made.

The bioprofiling of antibacterials in olive leaf extracts via thin layer chromatography-effect directed analysis (TLC-EDA).

In this study, effect-directed analysis (EDA) (i.e. TLC hyphenated with an in situ MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) antimicrobial assay), was used for screening and identification of antimicrobials in olive leaf extract. EDA detected that the same compounds exhibited significant antimicrobial activity against bacterial species of the genera Enterococcus (E. faecalis), Escherichia (E. coli), Streptococcus (S. mutans) and Staphylococcus (S. aureus). Flash chromatography-fractionation was used to isolate antimicrobial compounds in olive leaf extract. The active compounds were identified as maslinic acid and oleanolic acid by comparing RF values of the detected active bands with the standard reference materials, with identity confirmed with NMR and ATR-FTIR spectroscopy. Maslinic and oleanolic acids were tested on the E. faecalis strain (which displayed the highest sensitivity in the MTT assay) to determine their inhibiting concentration 50% (IC50) and minimum bactericidal concentrations.

Determination of the ursolic and oleanolic acids content with the antioxidant capacity in apple peel extract of various cultivars.

Apples are rich sources of ursolic acid (UA) and oleanolic acid (OA) which are the major and most prominent triterpenes in the peel of an apple. Pentacyclic triterpenes are ideal nutraceuticals due to their ability to reduce the risk of many life-threatening diseases such as cancer, cardiovascular and diabetes. This study was to determine the content of UA and OA in the apple peel extract from different cultivars grown in South Africa as well as the correlation of their content level with antioxidant capacity. Quantitative analysis of UA and OA in apple peels from three cultivars; red delicious (RD), royal gala (RG) and granny smith (GS) apples was carried out using HPLC and their antioxidant capacity was analyzed using the DPPH assay. The RD showed the highest content of UA and OA (248.02 ± 0.08 µg/ml and 110.00 ± 0.08 µg/ml respectively) in the apple peel extract and also displayed a significantly high level of antioxidant capacity (97.3 ± 0.40%; p < 0.0001) compared to the RG and GS cultivars. A strong positive correlation was noted between the UA, OA and antioxidant capacities of all the cultivars. Only the RD cultivar showed a significant correlation though; UA (r = 0.9570; p = 0.0027) and OA (r = 0.8503; p = 0.0319). This study demonstrated that the RD and RG apple peels possess the highest UA and OA content which invariably increases their antioxidant activities compared to GS apple. Thus, both apple cultivars would be useful and recommended for food consumption and nutraceuticals values to improve human health.

Identification of Corosolic and Oleanolic Acids as Molecules Antagonizing the Human RORγT Nuclear Receptor Using the Calculated Fingerprints of the Molecular Similarity.

RORγT is a protein product of the RORC gene belonging to the nuclear receptor subfamily of retinoic-acid-receptor-related orphan receptors (RORs). RORγT is preferentially expressed in Th17 lymphocytes and drives their differentiation from naive CD4+ cells and is involved in the regulation of the expression of numerous Th17-specific cytokines, such as IL-17. Because Th17 cells are implicated in the pathology of autoimmune diseases (e.g., psoriasis, inflammatory bowel disease, multiple sclerosis), RORγT, whose activity is regulated by ligands, has been recognized as a drug target in potential therapies against these diseases. The identification of such ligands is time-consuming and usually requires the screening of chemical libraries. Herein, using a Tanimoto similarity search, we found corosolic acid and other pentacyclic tritepenes in the library we previously screened as compounds highly similar to the RORγT inverse agonist ursolic acid. Furthermore, using gene reporter assays and Th17 lymphocytes, we distinguished compounds that exert stronger biological effects (ursolic, corosolic, and oleanolic acid) from those that are ineffective (asiatic and maslinic acids), providing evidence that such combinatorial methodology (in silico and experimental) might help wet screenings to achieve more accurate results, eliminating false negatives.

Cytotoxic 13,28 Epoxy Bridged Oleanane-Type Triterpenoid Saponins from the Roots of Ardisia crispa.

Ardisiacrispin D-F (1-3), three new 13,28 epoxy bridged oleanane-type triterpenoid saponins, together with four known analogues (4-7) were isolated from the roots of Ardisia crispa. The structures of 1-7 were elucidated based on 1D and 2D-NMR experiments and by comparing their spectroscopic data with values from the published literatures. Ardisiacrispin D-F (1-3) are first examples that the monosaccharide directly linked to aglycone C-3 of triterpenoid saponins in genus Ardisia are non-arabinopyranose. In the present paper, all compounds are evaluated for the cytotoxicity against three cancer cell lines (HeLa, HepG2 and U87 MG) in vitro. The results show that compounds 1, 4 and 6 exhibited significant cytotoxicity against Hela and U87 MG cells with IC50 values in the range of 2.2 ± 0.6 to 9.5 ± 1.8 µM. The present investigation suggests that roots of A. crispa could be a potential source of natural anti-tumor agents and their triterpenoid saponins might be responsible for cytotoxicity.

Saponin constituents of Achyranthes root.

Achyranthes root is a crude drug used as diuretic, tonic and remedy for blood stasis. Characteristic oleanolic acid saponins with a dicarboxylic acid moiety have been isolated as one of the representative constituents of this crude drug. This review focuses on the triterpene saponin constituents, especially those with a characteristic dicarboxylic acid moiety, of A. bidentata and A. fauriei. Several groups isolated the saponins and different names were given to one compound in some cases. The names of the compounds are sorted out and the stereochemistry of the dicarboxylic acid moieties are summarized. HPLC analysis of the composition of the saponin constituents and the effect of processing and extraction conditions on the composition are reviewed. Biological activities of the saponin constituents are also summarized.

A new oleanane-skeleton triterpene isolated from Coffea canephora.

Extensive fractionation of n-hexane extract from the dried powdered-trunks of Coffea canephora Pierre ex A.Froehner (Rubiaceae) led to the isolation of a new oleanane-skeleton triterpene, coffecanolic acid (1), along with three known analogues sumaresinolic acid (2), oleanolic acid (3), and 3-O-acetyloleanolic acid (4). The chemical structures were elucidated using FT-IR, 1D and 2D NMR and HR-ESI-MS data analysis. The isolated compounds were assayed for in vitro α-glucosidase inhibitory activity by determining their half-maximal inhibitory concentration (IC50, µM). Compounds 1-4 exhibited higher inhibitory activities when compared with acarbose, a positive control. Compound 1 was found to be the most potent molecule against α-glucosidase, with the IC50 = 83.0 ± 1.2 µM, which improved by 2.5-fold over acarbose (IC50 = 209.8 ± 0.3 µM) in this assay.[Formula: see text].

α-Amyrin and ß-Amyrin Isolated from Celastrus hindsii Leaves and Their Antioxidant, Anti-Xanthine Oxidase, and Anti-Tyrosinase Potentials.

Celastrus hindsii is a popular medicinal plant in Vietnam and Southeast Asian countries as well as in South America. In this study, an amount of 12.05 g of an α-amyrin and ß-amyrin mixture was isolated from C. hindsii (10.75 g/kg dry weight) by column chromatography applying different solvent systems to obtain maximum efficiency. α-Amyrin and ß-amyrin were then confirmed by gas chromatography-mass spectrometry (GC-MS), electrospray ionization-mass spectrometry (ESI-MS), and nuclear magnetic resonance (NMR). The antioxidant activities of the α-amyrin and ß-amyrin mixture were determined via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays with IC50 of 125.55 and 155.28 µg/mL, respectively. The mixture exhibited a high potential for preventing gout by inhibiting a relevant key enzyme, xanthine oxidase (XO) (IC50 = 258.22 µg/mL). Additionally, an important enzyme in skin hyperpigmentation, tyrosinase, was suppressed by the α-amyrin and ß-amyrin mixture (IC50 = 178.85 µg/mL). This study showed that C. hindsii is an abundant source for the isolation of α-amyrin and ß-amyrin. Furthermore, this was the first study indicating that α-amyrin and ß-amyrin mixture are promising in future therapies for gout and skin hyperpigmentation.

Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia.

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.

Molecularly imprinted solid-phase extraction of Chikusetsu saponin IVa from Panacis majoris Rhizoma.

As the main active component of Panacis majoris Rhizoma, Chikusetsu saponin IVa has the activity of anti-oxidation, anti-inflammatory pain, and so on. Obtaining high purity Chikusetsu saponin IVa by simple purification steps is a prerequisite for its deep development. In this paper, the separation and purification of Chikusetsu saponin IVa were studied by molecular imprinting technique. By ultraviolet and visible spectrophotometry and computer molecular simulation, it was concluded that water-soluble 3-(2-carboxyethyl)-1-vinylimidazolium bromide ionic liquid was the best functional monomer compared with acrylic acid and acrylamide. The molecularly imprinted polymers were prepared by precipitation polymerization at 60℃ with Chikusetsu saponin IVa as template molecule, 3-(2-carboxyethyl)-1-vinylimidazolium bromide as functional monomer, ethylene glycol dimethacrylate as cross-linker, 2, 2'-azobisisobutyronitrile as initiator, and ethanol as porogen. The properties of molecularly imprinted polymers were studied by scanning electron microscopy, Fourier transform infrared spectroscopy, thermo-gravimetric analysis, nitrogen adsorption/desorption isotherm, and X-ray photoelectron spectroscopy. The maximum adsorption capacity was 171.33 mg/g, and the imprinting factor was 2.6. Finally, the polymers can be successfully used in the purification of Chikusetsu saponin IVa from Panacis majoris Rhizoma through a simple procedure, the content was significantly increased. The recoveries of the spiked samples for the CS-IVa ranged from 94.05 to 99.95% with relative standard deviation values lower than 2.67%. The results showed that the polymers demonstrated good adsorption capacity for Chikusetsu saponin IVa. Meanwhile, the polymers showed great stability and reusability during the application.

Metabolite profiling of Shuganzhi tablets in rats and pharmacokinetics study of four bioactive compounds with liquid chromatography combined with electrospray ionization tandem mass spectrometry.

Shuganzhi Tablets (SGZT) is developed on the basis of a clinical empirical formula as a hospital preparation for the treatment of fatty liver. In this study, a rapid and highly sensitive LC-MS/MS method was established and validated for simultaneous determination of ginsenoside Re, ginsenoside Rg1, notoginsenoside R1, naringin, specnuezhenide, emodin, polydatin, hesperidin and saikosaponin A in rat plasma. Multiple reaction monitoring mode played an important role in simultaneous quantitative analysis of multiple components. The analytes were separated by the action of an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) in five minutes. The validated LC-MS/MS method was successfully applied to the pharmacokinetic analysis of hesperidin, emodin, polydatin and naringin of SGZT in rat plasma after administration. A UHPLC system couple with a quadrupole combined with time of flight mass spectrometer was used for qualitatively analyzing of the composition of SGZT and its metabolites in serum, urine, bile and feces of rats. The results showed that a total of 65 components were detected in rat biological samples, including 10 prototype components and 55 metabolites. It was speculated that the ingredients of SGZT experienced mainly the following reactions in rats: phase I reaction such as hydrolysis, oxidation, hydroxylation, carboxylation and dehydroxylation and phase Ⅱ reaction such as glucuronidation and sulfation. These results provide useful information for the further study of its active ingredients.

Role of taraxerone isolated from Leucas lavandulifolia, as an immunomodulator.

ETHNOPHARMACOLOGICAL RELEVANCE: The Indian tradition system of medicine enlists a large number of plants for basic health care. Leucas lavandulifolia is mentioned in the ayurvedic medicinal system and also used among the folklores. The plant is used for the treatment of fever, asthma, psoriasis, dermatitis and healing snake bites. The scientific validation of the plant for their traditional use in different immune related disorders are yet to be explored. AIM OF THE STUDY: The study aims to isolate immunomodulatory active compound from Leucas lavandulifolia and evaluating its efficiency in immune related disorders. MATERIALS AND METHODS: The immunomodulatory activity of the phytocompound is evaluated through in vitro and in vivo studies. The compound purification and identification were done by chromatography and LC/Q-TOF respectively. Its immunomodulatory activity was evaluated in cells like PBMC, neutrophils and macrophages by MTT assay and cell cycle analysis. Animal studies were performed on Swiss albino mice. The levels of IL-4 and IL-6 cytokines were also evaluated in both in vitro and in vivo models. RESULTS: Leucas lavandulifolia stem portion was found to have good modulatory property. An active immunomodulator was isolated from the methanol extract of the plant. LC/Q-TOF data revealed the isolated compound to be taraxerone. In PBMC, the compound was capable of suppressing the proliferation rate of the compound indicated by a decrease in cell numbers. The activated IL-4 and IL-6 production was also suppressed actively at 25 µg/ml of taraxerone. Similar inhibitory effects were seen in RAW 264.7 and THP-1 macrophage cell lines. An IC50 value of 17.5 µg/ml was obtained for taraxerone in LPS stimulated RAW 264.7 macrophage cell lines. The NO level, IL-4, IL-6 and phagocytosis in the LPS stimulated macrophage was effectively lowered by 25 µg/ml of taraxerone. In PMA stimulated THP-1 Macrophage Cell Lines, taraxerone was capable of suppressing the cell number and IL-6. The compound didn't show any effect on IL-4 levels. The compound exhibited an immunosuppressive activity in PHA induced PMN cells by suppressing the respiratory burst and interleukins IL-4 and IL-6. TX could also suppress the proliferation of DNCB induced monocyte cells and IL-4. The haematological parameters exhibited a significant suppression for the high dose group of taraxerone. The antibody titre and phagocytic index was suppressed by the high dose group, whereas the low dose group did not have any effect. So taraxerone at 50 mg/kg body weight is capable of modulating the B-lymphocytes and macrophages. But the compound has exhibited insignificant effect on the DTH hypersensitivity response and organ index. CONCLUSION: Taraxerone at high concentration was capable of suppressing stimulated PBMC, macrophage and PMN. The activated nitric oxide, IL-4, IL-6 production and phagocytosis was also suppressed. The haematological parameters, antibody titre and phagocytic index was also lowered in antigenically challenged mice. The terpenoid taraxerone exhibits a good modulatory effect on the immune system and proves to be a potent drug for the treatment of many allergic disorders.

Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases.

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).

Design, Synthesis, Molecular Modelling, and Biological Evaluation of Oleanolic Acid-Arylidene Derivatives as Potential Anti-Inflammatory Agents.

INTRODUCTION: Oleanolic acid, a pentacyclic triterpenic acid, is widely distributed in medicinal plants and is the most commonly studied triterpene for various biological activities, including anti-allergic, anti-cancer, and anti-inflammatory. METHODS: The present study was carried out to synthesize arylidene derivatives of oleanolic acid at the C-2 position by Claisen Schmidt condensation to develop more effective anti-inflammatory agents. The derivatives were screened for anti-inflammatory activity by scrutinizing NO production inhibition in RAW 264.7 cells induced by LPS and their cytotoxicity. The potential candidates were further screened for inhibition of LPS-induced interleukin (IL-6) and tumour necrosis factor-alpha (TNF-α) production in RAW 264.7 cells. RESULTS: The results of in vitro studies revealed that derivatives 3d, 3e, 3L, and 3o are comparable to that of the oleanolic acid on the inhibition of TNF-α and IL-6 release. However, derivative 3L was identified as the most potent inhibitor of IL-6 (77.2%) and TNF-α (75.4%) when compared to parent compound, and compounds 3a (77.18%), 3d (71.5%), and 3e (68.8%) showed potent inhibition of NO than oleanolic acid (65.22%) at 10µM. Besides, from docking score and Cyscore analysis analogs (3e, 3L, 3n) showed greater affinity towards TNF-α and IL-1ß than dexamethasone. CONCLUSION: Herein, we report a series of 15 new arylidene derivatives of oleanolic acid by Claisen Schmidt condensation reaction. All the compounds synthesized were screened for their anti-inflammatory activity against NO, TNF-α and IL-6. From the data, it was evident that most of the compounds exhibited better anti-inflammatory activity.