Tormentic Acid Research Articles (Page 1)

Unlocking the therapeutic potential: Comparative analysis of tormentic acid and its ester in combating inflammation and oxidative stress

3-O-trans-p-coumaroyl esterification enhances the anti-inflammatory effects of tormentic acid by targeting NF-κB signaling.

Diabetic nephropathy (DN) represents a severe microvascular complication of diabetes mellitus. As a Traditional Chinese Medicine (TCM) with extensive clinical applications, Ligustri Lucidi Fructus (LLF) exhibits significant anti-DN activity. However, the underlying pharmacological mechanisms, crucial components, and targets for LLF in DN treatment remain unclear. By integrating network pharmacology, molecular docking, and molecular dynamics simulations, the bioactive compounds, potential therapeutic targets, and underlying mechanisms of LLF in the treatment of DN were elucidated, followed by biological validation in a palmitic acid (PA)-induced MPC5 podocyte injury model. Among the 383 DN-related LLF targets identified, TNF emerged as a pivotal one, demonstrating potential binding interaction with the active components salidroside (Sal), apigenin (Api), and tormentic acid (TA). Moreover, Gene Expression Omnibus (GEO) database and KEGG enrichment analysis collectively highlighted the cytosolic DNA-sensing pathway. Notably, the cGAS-STING pathway is central to this pathway. Experimental studies further demonstrated that LLF-containing serum exerted a protective effect on MPC5 podocytes through cGAS-STING pathway suppression. Overall, these findings elucidate the pleiotropic mechanisms underlying LLF's protective effects against DN, integrating compound-target-pathway interactions and thus offering a rationale for further investigation.

The study aimed to investigate the anti-aging, skin-whitening, and antioxidant capacities of the extracts and constituents from the roots of Rosa canina L. by anti-collagenase, anti-tyrosinase activity, ferric-reducing antioxidant power (FRAP), cupric-reducing antioxidant capacity (CUPRAC) assays, and the Folin-Ciocalteu method (for the extracts). Enzyme inhibitory activities, pharmacokinetics, and drug-likeness properties of the compounds were evaluated in silico. According to the results of activity studies, the ethyl acetate subextract exhibited the highest anti-tyrosinase activity, and the remaining aqueous subextract demonstrated the highest anti-collagenase activity. The isolation studies led to the purification of euscaphic acid (1), tormentic acid (2), kaji-ichigoside F1 (3), rosamultin (4), 2-oxopomolic acid (5), and (+)-catechin (6) for the first time from the roots of this plant. Isolated compounds exhibited anti-collagenase and anti-tyrosinase activities. The extracts and (+)-catechin had higher antioxidant capacities than other compounds. R. canina roots and their compounds can be included in dermocosmetic products after further studies.

Leaves of Eriobotrya japonica have long been utilized in traditional Chinese medicine (TCM) for treating pulmonary inflammation and stomach disorders. This study extends their pharmacological applications by evaluating the antioxidant, anti-α-glucosidase, anti-acetylcholinesterase (AChE), and anti-inflammatory activities of solvent extracts and isolated bioactive components through an integrative approach combining extraction, bioassays, and molecular docking. Solvent extracts prepared with varying polarities exhibited distinct bioactivities, with the 100 °C water and methanol extracts displaying the strongest antioxidant potential. The ethyl acetate extract exhibited potent α-glucosidase inhibition, whereas the n-hexane extract demonstrated significant AChE inhibitory activity. Among the isolated compounds, epicatechin (5) (SC50 = 7.83 ± 0.34 μM) and rutin (6) (SC50 = 6.69 ± 0.25 μM) showed superior ABTS and superoxide scavenging activities, respectively, compared to the positive controls (BHT and cynaroside). Ursolic acid (2) exhibited stronger α-glucosidase inhibition (IC50 = 10.68 ± 0.76 μM) than acarbose (IC50 = 419.93 ± 29.15 μM), while tormentic acid (4) demonstrated superior AChE inhibition compared to chlorogenic acid. Ursolic acid (2) also displayed NO inhibition (IC50 = 20.18 ± 1.46 μM) comparable to quercetin (IC50 = 17.05 ± 1.63 μM), with Western blot analysis confirming its potent iNOS inhibitory activity. Molecular docking further supported these findings, revealing that ursolic acid (2) exhibited stronger binding affinity to α-glucosidase (-8.7 kcal/mol) than acarbose (-5.1 kcal/mol), tormentic acid (4) displayed higher binding energy to AChE (-8.8 kcal/mol) compared to chlorogenic acid (-7.8 kcal/mol), and ursolic acid (2) (-7.5 kcal/mol) showed a binding affinity to iNOS similar to that of quercetin (-7.7 kcal/mol). These results highlight the strong potential of E. japonica leaf extracts and bioactive compounds as natural antioxidants, enzyme inhibitors, and anti-inflammatory agents, supporting their development as dietary supplements or therapeutic candidates for managing oxidative stress, hyperglycemia, neurodegenerative diseases, and inflammatory disorders.

Chronic kidney disease (CKD) progresses through mechanisms involving inflammation, fibrosis, and oxidative stress, leading to the gradual structural and functional deterioration of the kidneys. Tormentic acid (TA), a triterpenoid compound with known anti-inflammatory and antioxidant properties, shows significant potential in counteracting these pathological processes. This study explored the protective role of TA in a unilateral ureteral obstruction (UUO)-induced CKD model. Mice received TA through intraperitoneal injections at a dosage of 5 mg/kg per day for 8 consecutive days, commencing a day before the UUO procedure. The TA treatment significantly improved both structural and functional kidney injury. It suppressed cytokine expression and reduced immune cell infiltration, inhibited the activation of the mitogen-activated protein kinase cascade, and alleviated endoplasmic reticulum stress. Moreover, TA displayed potent anti-fibrotic effects by reversing epithelial-to-mesenchymal transition and inhibiting Smad2/3 activation, reducing extracellular matrix deposition. TA also mitigated oxidative stress by attenuating lipid peroxidation and boosting antioxidant defenses. Additionally, it inhibited apoptosis and ferroptosis by reducing oxidative stress and modulating key cell death markers. Collectively, these findings indicate that TA provides comprehensive renoprotection in the UUO model by effectively targeting inflammation, fibrosis, oxidative stress, and tubular cell death in CKD progression.

In this study, a phytochemical investigation on the methanol extract of Potentilla chinensis led to the isolation of eleven triterpenoids including ursolic acid (1), pomolic acid (2), tormentic acid (3), 2-epi-corosolic acid (4), 3-epi-corosolic acid (ECA, 5), 3β-hydroxyurs-11-en-13β(28)-olide (6), euscaphic acid (7), 2-epi-tormentic acid (8), corosolic acid (9), uvaol (10), and 3-O-acetylpomolic acid (11). Among them, ECA (5) showed potential anti-osteoclastogenic activity. To the best of our knowledge, this represents the first isolation of ECA (5) from P. chinensis as well as the first investigation of its effects on osteoclast formation. Further study revealed that ECA inhibited RANKL-induced mature osteoclast formation in vitro without compromising cell viability. Mechanistically, ECA attenuated RANKL-induced mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation, leading to the inhibition of c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) activation. Moreover, ECA protected against LPS-induced inflammatory bone loss and osteoclast formation in a mouse model. However, ECA did not inhibit LPS-induced inflammatory responses in macrophages. Our findings suggest that ECA mitigates LPS-induced inflammatory bone loss in mice by inhibiting RANKL-induced activation of key osteoclastogenic transcription factors, including c-Fos and NFATc1, and may be a potential natural triterpenoid for preventing or treating osteolytic diseases.

Cloudberry (Rubus chamaemorus L.) is a plant rich in various biologically active compounds. In this work, the composition and concentrations of pentacyclic triterpenoids (PCTs) and phytosterols in various parts of cloudberries were studied using high-performance liquid chromatography-tandem mass spectrometry by multiple reaction monitoring mode (MRM, targeted analysis) and precursor ion scan mode (non-targeted analysis and semi-quantitative determination). Moderately polar fractions of cloudberry leaves, sepals and berries extracts are rich in β-sitosterol glycoside and various triterpenoid acids, among which tormentic acid (∼190-1800 μg/g dw part of cloudberries) and its hydroxyl derivatives (∼3.1-470 μg/g dw part of cloudberries) predominate. Non-polar fractions are characterised by the presence of amyrins (0.76-110 μg/g dw part of cloudberries), β-sitosterol (62-750 µg/g dw part of cloudberries) and β-sitosterol glycoside (∼92-360 μg/g dw sepals).

Purification and structural analysis of β-glucosidase from Lactobacillus acidophilus GIM1.208 and its interaction with rosamultin in Rosa roxburghii Tratt

Introduction: Diabetes mellitus is an endocrine disorder characterized by hyperglycemia, glycosuria, and hyperlipidemia. various plants are used as natural antidiabetics. Objective: to know plants that are efficacious as antidiabtes as an alternative in the treatment of diabetes mellitus. Methods: literature review. Data sources came from research journals on plants that are efficacious as antidiabetics from national and international sources. The data search strategy used was to search the literature directly through the Google search engine and use the Google Scholar, Pubmed, and Science Direct databases with the keywords “plants that are efficacious as antidiabetics”, “secondary metabolites of plants as antidiabetics”. Inclusion criteria included national journals on the efficacy of sungkai plants with Sinta accreditation 1-6, and Scopus indexed international journals with Q1- Q4 rankings. Exclusion criteria included journals that did not focus on plants as antidiabetics and journals that were not accredited. Results: Results: From the reviewed national and international journals, it was found that various plants have antidiabetic properties and have been tested for safety in animal experiments and traditionally by the community. Conclusion: Based on the literature that has been collected, it can be concluded that there have been many studies on plants that are efficacious as antidiabetics ranging from Kumis Kucing plant, pegagan plant, red betel leaves, and various other plants that have been studied experimentally, the content of quercetin, pomolic acid, tormentic acid, and eucalyptus acid with different mechanisms of action from each other contained in these plants plays a role in reducing blood sugar levels.

Diminished ovarian reserve has a serious impact on female reproduction with an increasing incidence every year. An important cause of this is oxidative stress. Rubi fructus, a traditional medicinal and edible plant, has shown therapeutic effects against gynecological diseases. Vanillic acid, isoquercitrin, kaempferol-3-O-rutinoside, kaempferol-3-O-sophoroside, oleanolic acid, tormentic acid, tiliroside, and ellagic acid are the major bioactive components in R. fructus. However, studies involved in the effectiveness and mechanism of these components in oxidative stress-induced ovarian dysfunction are scarce. In this study, the protective mechanisms of the bioactive components were evaluated in human ovarian granulosa cells. Isoquercitrin was significantly superior to other bioactive components in relieving damage in human ovarian granulosa cells induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride, considering enhanced cell viability, reduced reactive oxygen species accumulation, and improved mitochondrial membrane potential level. Isoquercitrin protected human ovarian granulosa cells from oxidative stress by regulating the enzyme activity of glutathione peroxidase, inhibiting cell apoptosis, improving the expression of genes related to oxidative stress, and ameliorating heme oxygenase 1 protein expression. Isoquercitrin, a bioactive component in R. fructus, has a significant protective effect on oxidative damage induced by 2,2-azobis (2-methylpropionamidine) dihydrochloride in human ovarian granulosa cells, providing evidence for its potential application in protecting ovarian function. © 2024 Society of Chemical Industry.

Self-formation of protective layer on carbon steel surface in 1 M HCl solution containing Barringtonia acutangula leaf extract

Plant extracts have been used to treat microbiological diseases for centuries. This study examined plant triterpenoids tormentic acid (TA) and 23-hydroxycorosolic acid (HCA) for their antibiofilm effects on Staphylococcus aureus strains (MTCC-96 and MTCC-7405). Biofilms are bacterial colonies bound by a matrix of polysaccharides, proteins, and DNA, primarily impacting healthcare. As a result, ongoing research is being conducted worldwide to control and prevent biofilm formation. Our research showed that TA and HCA inhibit S. aureus planktonic growth by depolarizing the bacterial membrane. In addition, zone of inhibition studies confirmed their effectiveness, and crystal violet staining and biofilm protein quantification confirmed their ability to prevent biofilm formation. TA and HCA exhibited substantial reductions in biofilm formation for S. aureus (MTCC-96) by 54.85% and 48.6% and for S. aureus (MTCC-7405) by 47.07% and 56.01%, respectively. Exopolysaccharide levels in S. aureus biofilm reduced significantly by TA (25μg/mL) and HCA (20μg/mL). Microscopy, bacterial motility, and protease quantification studies revealed their ability to reduce motility and pathogenicity. Furthermore, TA and HCA treatment reduced the mRNA expression of S. aureus virulence genes. In silico analysis depicted a high binding affinity of triterpenoids for biofilm and quorum-sensing associated proteins in S. aureus, with TA having the strongest affinity for TarO (-7.8kcal/mol) and HCA for AgrA (-7.6kcal/mol). TA and HCA treatment reduced bacterial load in S. aureus-infected peritoneal macrophages and RAW264.7 cells. Our research indicates that TA and HCA can effectively combat S. aureus by inhibiting its growth and suppressing biofilm formation.

Cancer is a mechanistically complex and diverse disease with a plethora of fundamental genetic and epigenetic factors. Signal transducer and activator of transcription-3 (STAT3) is a transcription factor, and its constitutive activation executes promotion of cellular proliferation, cell cycle, angiogenesis, metastasis, immunosuppression, and chemo-resistance in cancer cells. Here, we aimed to design natural potential STAT3 inhibitors. For this purpose, we investigated 92 phytochemical compounds by molecular docking studies because they are diversified, multitargeted, affordable, easily available, and less- or non-toxic. We selected only 6 compounds such as sarsasapogenin (L3), peiminine (L9), solasodine (L10), tormentic acid (L23), obacunone (L29), and echinocystic acid (L34) due to their greater binding affinity than reference STAT3 inhibitor (S3I-201) with STAT3. The study was further continued by molecular dynamic (MD) simulations and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The results of molecular docking showed that all selected ligands exhibited binding affinity range from -9.3 Kcal/mol to -7.9 Kcal/mol and predicted inhibition constant ([Formula: see text].) values range from 0.14 [Formula: see text]M to 1.5 [Formula: see text]M. These compounds showed effective hydrogen bonding and hydrophobic interactions with DNA binding domain as well as SH2-domain of STAT3. The MD simulations performed by nanoscale molecular dynamics (NAMD) calculated root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration ([Formula: see text]), solvent accessible surface area (SASA) and number of hydrogen bond dynamics. All selected ligands with protein exhibited stability over 120 ns by MD simulation. Moreover, these ligands showed favorable ADMET profiling and drug likeness. So, our current computational investigations showed that these novel drug candidates can be potential STAT3 inhibitors and evoke the scientific interest for their further verification by in vitro and in vivo studies.

Enzyme immobilized on magnetic fluorescent bifunctional nanoparticles for α-glucosidase inhibitors virtual screening from Agrimonia pilosa Ledeb extracts accompanied with molecular modeling

Context Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. Objective To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. Materials and methods TA concentrations of 1.563–25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. Results TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. Discussion and conclusions TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.

The phytochemical investigation of the aqueous methanolic extract of the aerial parts of Dioscorea preussii, led to the isolation of a new chalcone preussiate (1) along with 10 other compounds including xanthomicrol (2), cholestan-3-one (3), arjunolic acid (4), tormentic acid (5), ursolic acid (6), betulin (7), lupeol (8), p-hydroxybenzoic acid (9), isovanillin (10) and vanillic acid (11), being reported for the first time from this plant. Their structures were established by spectroscopic techniques including 2D NMR spectroscopy. All the isolates were subjected to the biological screening but only showed antioxidant and urease inhibitory properties. The compounds 1,8 and 11 displayed the most potent urease inhibitory properties with IC50 values, 22.4, 33.3 and 35.7 µM, respectively, while 3 was moderately active. The compound 11 showed potent antioxidant activity among all the tested isolates with an IC50 value of 45.3 µM.

Antimicrobial and in silico studies of the triterpenoids of Dichapetalum albidum

Rosae Radix et Rhizoma is a herbal medicine in a variety of famous Chinese patent medicines, while the quality standard for this medicine remains to be developed due to the insufficient research on the quality of Rosae Radix et Rhizoma from different sources. Therefore, this study comprehensively analyzed the components in Rosae Radix et Rhizoma of different sources from the aspects of extract, component category content, identification based on thin-lay chromatography, active component content determination, and fingerprint, so as to improve the quality control. The results showed that the content of chemical components varied in the samples of different sources, while there was little difference in the chemical composition among the samples. The content of components in the roots of Rosa laevigata was higher than that in the other two species, and the content of components in the roots was higher than that in the stems. The fingerprints of triterpenoids and non-triterpenoids were established, and the content of five main triterpenoids including multiflorin, rosamultin, myrianthic acid, rosolic acid, and tormentic acid in Rosae Radix et Rhizoma was determined. The results were consistent with those of major component categories. In conclusion, the quality of Rosae Radix et Rhizoma is associated with the plant species, producing area, and medicinal parts. The method established in this study lays a foundation for improving the quality standard of Rosae Radix et Rhizoma and provides data support for the rational use of the stem.

Bioassay-guided isolation of antimycobacterial compounds from Aphloia theiformis (Vahl) Benn root ethanolic extract