Natural Triterpene Research Articles

Sorafenib, a Tyrosine Kinase Inhibitor, Synergistically Enhances the Ferroptosis Effects of Asiatic Acid in Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide. Asiatic acid (AA) is a natural triterpene, which is recognized as effect of antioxidant and antitumor. Sorafenib (Sor), an orally target drug, has been applicate for the HCC therapy. However, the synergistic effect of AA and Sor on human HCC is still unclear. Here, we explore the effect of combined treatment with AA and Sor in the HCC cell line SK-HEP-1 and HepG2. Compared with treating alone, our results demonstrated that AA combined with Sor synergistically inhibited proliferative rates in MTT assay and colony formation assay. We also found that AA combined with Sor in HCC cells strongly caused cell cycle arrest in G0/G1 phase and affected the protein level of cyclin D1 and SKP2. Furthermore, combination treatment strongly enhanced ferroptosis through cellular accumulation of iron ions, lipid peroxidation, and ferroptosis-related proteins (GPX4 and FTH1) in HCC cells. In addition, the combined treatment resulted in higher phosphorylation of JNK1/2 in the promotion of ferroptosis than drug treatment alone. These results indicate that AA combined with Sor synergistically improved ferroptosis in HCC cells through the regulation of JNK1/2 signaling. Taken together, the combinatorial strategy may serve as the potential treatment in HCC.

Improving Water Solubility and Skin Penetration of Ursolic Acid through a Nanofiber Process to Achieve Better In Vitro Anti-Breast Cancer Activity.

Woman's breast cancer has always been among the top ten causes of cancer death, and nearly 2% to 5% of locally advanced breast cancers develop a fungating breast wound. Fungal breast cancer leads to skin ulcers, wound ruptures, and other bacterial infections in patients. Ursolic acid (UA), a natural pentacyclic triterpene compound, is widely distributed in many fruits. Previous studies demonstrated that UA has anti-breast cancer, antifungal, and improved wound-healing effects. UA, however, had poor water solubility and low bioavailability, restricting its clinical application. Nanofibers have the advantages of rapid dissolution, improved stability, and bioavailability of active ingredients. We had successfully prepared ursolic acid nanofibers (UANFs) and effectively improved their water solubility and skin penetration. UANFs can increase water solubility by improving the physicochemical properties, including increased surface area, intermolecular bonding with excipients, and amorphous transformation. Furthermore, UANFs had better anti-breast cancer activity than raw UA. UANFs inhibited the expression of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho-extracellular regulated protein kinases (ERK)1/2, and induced cleaved caspase-3 protein expression, but had no effect on the raw UA treatment. In summary, UANFs enhanced the skin absorption of UA and improved its anti-breast cancer efficacy. We expect that UANFs can be used as an anti-breast cancer treatment and reduce the discomfort of breast cancer patients during dressing changes, but more detailed efficacy and safety trials still need to be conducted in further studies.

The anti-cancer mechanism of Celastrol by targeting JAK2/STAT3 signaling pathway in gastric and ovarian cancer

BackgroundCelastrol is a natural triterpene exhibiting significant and extensive antitumor activity in a wide range of cancer. Due to unfavorable toxicity profile and undefined mechanism, Celastrol's application in clinical cancer therapy remains limited. Herein, we elucidate the pharmacological mechanism of Celastrol's anticancer effects, with a focus on STAT3 signaling pathway in cancers with high incidence of metastasis. MethodsThe safety profile of Celastrol were assessed in mice. In vitro analysis was performed in gastric cancer and ovarian cancer to assess the cytotoxicity, induction of reactive oxygen species (ROS) of Celastrol using STAT3 knockout cancer cells. Effects of Celastrol on STAT3 activation and transcription activity, JAK2/STAT3 signaling protein expression were assessed. Additionally, proteomic contrastive analysis was performed to explore the molecular association of Celastrol with STAT3 deletion in cancer cells. ResultsCelastrol has no obvious toxic effect at 1.5 mg/kg/day in a 15 days' administration. Celastrol inhibits tumor growth and increases ROS in a STAT3 dependent manner in gastric and ovarian cancer celllines. On molecular level, it downregulates IL-6 level and inhibits the JAK2/STAT3 signaling pathway by suppressing STAT3’ activation and transcription activity. Proteomic contrastive analysis suggests a similar cellular mechanism of action between Celastrol and STAT3 deletion on regulating cancer progression pathways related to migration and invasion. ConclusionOur research elucidates the anti-cancer mechanism of Celastrol through targeting the JAK2/STAT3 signaling pathway in cancer with high incidence of metastasis. This study provides a solid theoretical basis for the application of Celastrol in cancer therapy.

Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives

The cytotoxic profile and antiproliferative and mitochondrial effects of triterpene acid conjugates with mitochondriotropic lipophilic triphenylphosphonium (TPP+) and F16 cations were evaluated. Maslinic and corosolic acids chosen as the investigation objects were synthesized from commercially available oleanolic and ursolic acids. Study of the cytotoxic activity of TPP+ and F16 triterpenoid derivatives against six tumor cell lines demonstrated a comparable synergistic effect in the anticancer activity, which was most pronounced in the case of MCF-7 mammary adenocarcinoma cells and Jurkat and THP-1 leukemia cells. The corosolic and maslinic acid hybrid derivatives caused changes in the progression of tumor cell cycle phases when present in much lower doses than their natural triterpene acid precursors. The treatment of tumor cell lines with the conjugates resulted in the cell cycle arrest in the G1 phase and increase in the cell population in the subG1 phase. The cationic derivatives of the acids were markedly superior to their precursors as inducers of hyperproduction of reactive oxygen species and more effectively decreased the mitochondrial potential in isolated rat liver mitochondria. We concluded that the observed cytotoxic effect of TPP+ and F16 triterpenoid conjugates is attributable to the ability of these compounds to initiate mitochondrial dysfunctions. Their cytotoxicity, antiproliferative action, and mitochondrial effects depend little on the type of cationic groups used.

Biomass betulin-based porous aromatic frameworks nanomicrospheres as adsorbents for reversible capture of iodine

Betulin with a modifiable hydroxyl group and a rigid backbone is a kind of natural triterpene product that extracted from white barked birch bark with up to 30 % of its dry weight. Herin, we prepared a series of betulin-based porous aromatic frameworks (BEPAFs) nanomicrospheres by [Rh(nbd)Cl]2 polymerization or Sonogashira-Hagihara coupling reaction for iodine vapor capture and adsorption. The resulting BEPAFs nanomicrospheres presented perfect thermal stability and high specific surface areas that up to 324.6 m2 g−1, 506.3 m2 g−1 and 320.5 m2 g−1 for BEPAF-1, BEPAF-2 and BEPAF-3, respectively. Based on the above characteristics, the BEPFAs nanomicrospheres showed an excellent iodine capture performance with the volatile iodine capture ability reached 3.79 g g−1 and iodine adsorption in cyclohexane solution up to 389.9 mg g−1. The iodine capture behavior is consistent with the pseudo-second-order model, indicating that the iodine adsorption process of BEPAFs microspheres belongs to multilayer heterogeneous surface chemical adsorption. Furthermore, the BEPFAs nanomicrospheres could maintained 88.26 % of the absorption capacity after four cycles that endow them a great potential in practical application. This research provides a facile synthesis of biomass porous aromatic framework nanomicrospheres adsorbents based on the natural product.

Uvaol alleviates oxidative stress induced human umbilical vein endothelial cell injury by suppressing mitogen-activated protein kinase signaling pathway.

Deep venous thrombosis (DVT) is a potentially life-threatening disorder with high morbidity. Uvaol is a natural pentacyclic triterpene possessing multiple pharmacological activities. Nevertheless, the role of uvaol in DVT is unclarified. Human umbilical vein endothelial cells (HUVECs) were treated with hydrogen peroxide (H 2 O 2 ) to mimic DVT in vitro . CCK-8 assay and flow cytometry were utilized for measuring cell viability and apoptosis, respectively. Levels of the cell injury marker, thrombosis-associated factors, inflammatory cytokines, and oxidative stress-related markers were examined by commercial assay kits. Western blotting was used for evaluating the expression of mitogen-activated protein kinase (MAPK) signaling-associated proteins. Uvaol treatment attenuated H 2 O 2 -induced HUVEC apoptosis and injury. Uvaol reduced the expression of pro-thrombotic factors and inflammatory cytokines and attenuated oxidative stress in H 2 O 2 -stimulated HUVECs. Uvaol inhibited MAPK signaling pathway in H 2 O 2 -stimulated HUVECs. Activating MAPK signaling reversed uvaol-mediated protective effects on H 2 O 2 -treated HUVECs. Uvaol treatment alleviates H 2 O 2 -induced HUVEC injury, apoptosis, and oxidative stress by inactivating MAPK signaling.

Tuning of the Anti-Breast Cancer Activity of Betulinic Acid via Its Conversion to Ionic Liquids.

Betulinic acid (BA) is a natural pentacyclic triterpene with diverse biological activities. However, its low water solubility limits its pharmaceutical application. The conversion of pharmaceutically active molecules into ionic liquids (ILs) is a promising strategy to improve their physicochemical properties, stability, and/or potency. Here, we report the synthesis and characterization of 15 novel ILs containing a cation ethyl ester of a polar, non-polar, or charged amino acid [AAOEt] and an anion BA. Except for [ValOEt][BA], we observed preserved or up to 2-fold enhanced cytotoxicity toward hormone-dependent breast cancer cells MCF-7. The estimated IC50 (72 h) values within the series varied between 4.8 and 25.7 µM. We found that the most cytotoxic IL, [LysOEt][BA]2, reduced clonogenic efficiency to 20% compared to that of BA. In addition, we evaluated the effect of a 72 h treatment with BA or [LysOEt][BA]2, the most cytotoxic compound, on the thermodynamic behavior of MCF-7 cells. Based on our data, we suggest that the charged amino acid lysine included in the novel ILs provokes cytotoxicity by a mechanism involving alteration in membrane lipid organization, which could be accompanied by modulation of the visco-elastic properties of the cytoplasm.

Ameliorative potential of β-sitosterol and lupeol on high fat diet and streptozotocin -induced hepatorenal and cardiac complications via regulation of carbohydrate metabolic enzymes in diabetic rats

Introductionβ-Sitosterol is a plant-derived compound that shares structural similarities with cholesterol and is used to treat coronary artery disease, prostate cancer, breast cancer, and hypercholesterolemia etc. Lupeol is a natural pentacyclic triterpene, found in a variety of fruits, vegetables, and traditional Chinese medicines like Astragalusmembranaceus and AtractylodesmacrocephalaKoidz. Numerous pharmacological activities of lupeol have been investigated; they include applications as antioxidant, antiviral, antihypertensive, anti-inflammatory and antitumor agents.The current study wasaimed to examine the potential benefits of β-sitosterol and lupeol in reducing pathophysiological complications caused by high fat diet and streptozotocin by regulating the enzymes involved in the metabolism of carbohydrates in diabetic rats as there was no study on this aspect. MethodsMale albino wistar rats were given a high-fat diet for two weeks in order to cause diabetes in them. Following a two-week period, the animals were administered a low dosage of streptozotocin and maintained on an overnight fast. Using commercial diagnostic kits, we assessed plasma glucose and glycated hemoglobin (HbA1C). Plasma insulin level was assayed with the help of an ELISA kit and other assays were made biochemically. ResultsThe homeostatic model of insulin resistance, glucose 6-phosphatase, fructose 1,6-bisphosphatase, and blood glucose levels all significantly increased in the diabetic rats, while plasma insulin, hexokinase, glucose 6-phosphate dehydrogenase, and glycogen content significantly decreased.In addition, the hepatic (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and renal (urea and creatinine) indicators in diabetic rats were raised, and their lipid profiles were disrupted. However, diabetic rats treated with lupeol and β-sitosterol significantly restored all these changed parameters to the levels close to normal. Furthermore, the treatment of lupeol and β sitosterol improved the liver, kidney and heart histology alteration to near normal and prevented the body weight loss. DiscussionBecause of its structural polymorphism, β-sitosterol appeared to be more effective than lupeol in all the parameters investigated and thus these results imply that β sitosterol is a more effective antidiabetic medication than lupeol.

Antcin-H, a natural triterpene derived from Antrodia cinnamomea, ameliorates dextran sulfate sodium-induced colitis in mice by inhibiting the NLRP3 inflammasome

Inflammatory bowel disease (IBD) comprises idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease. Patients with IBD experience a significantly reduced quality of life, and effective management remains challenging. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome controls the expression of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Abnormal activation of the NLRP3 inflammasome is a crucial factor in the pathogenesis of IBD, making it an attractive therapeutic target. We discovered that Antcin-H, a triterpene isolated from the unique medicinal fungus Antrodia cinnamomea found in Taiwan, effectively inhibits the NLRP3 inflammasome in macrophages and alleviates dextran sulfate sodium (DSS)-induced colitis in a mouse model. We noted that Antcin-H effectively suppresses the NLRP3 inflammasome in macrophages by diminishing reactive oxygen species production, alleviating mitochondrial damage, and reducing apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. Importantly, these effects are achieved without impacting NF-κB activation. Oral administration of Antcin-H improved symptoms such as diarrhea, bloody stool, weight loss, colon length shortening, and splenomegaly in DSS-treated mice. Antcin-H inhibits colonic expression of NLRP3, ASC, active caspase-1, IL-1β, IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, myeloperoxidase, C-X-C motif chemokine ligand 1, and cyclooxygenase-2 in DSS-treated mice. Furthermore, Antcin-H modulates the colonic expression of long non-coding RNAs involved in the regulation of NLRP3 inflammasome activation. These results indicate that Antcin-H has the potential to improve IBD by reducing colonic inflammation and suppressing NLRP3 inflammasome activation.

Ursonic acid attenuates spermatogenesis in oligozoospermia mice through inhibiting ferroptosis

Ursonic acid (UNA) is a natural pentacyclic triterpene found in some medicinal plants and foods. The reproductive protective effect of UNA was evaluated in a mouse model of oligozoospermia induced by busulfan (BUS) at 30 mg/kg b.w.. The mice were initially divided into groups with UNA concentrations of 10, 30, 50, 100 mg/kg. Subsequently, based on sperm parameters, the optimal concentration of 50 mg/kg was identified. As a control, an additional group was supplemented with ursolic acid at a concentration of 50 mg/kg. The results indicated that BUS caused the loss of spermatogenic cells in testis, the decrease of sperm in epididymis, the disorder of testicular cytoskeleton, the decrease of serum sex hormones such as testosterone which induced an increase in feedback of androgen receptor and other testosterone-related proteins, the increase of malondialdehyde and reactive oxygen species levels and the increase of ferroptosis in testis while UNA successfully reversed these injuries. High-throughput sequencing revealed that UNA administration significantly upregulated the expression of genes associated with spermatogenesis, such as Tnp1, Tnp2, Prm1, among others. These proteins are crucial in the histone to protamine transition during sperm chromatin remodeling. Network pharmacology analysis reveals a close association between UNA and proteins related to the transformation of histones to protamine. Molecular docking studies reveal that UNA can interact with the ferroptosis-inhibiting gene SLC7A11, thereby modulating ferroptosis. Taken together, UNA alleviated BUS-induced oligozoospermia by regulating hormone secretion, mitigating oxidative stress and promoting recovery of spermatogenesis by inhibiting the ferroptosis.

Glycyrrhizin attenuates myocardial ischemia reperfusion injury by suppressing Inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway

Ferroptosis, a form of regulated cell death process, play an important role in myocardial ischemia‒reperfusion (I/R) injury. Glycyrrhizin (GL), a natural glycoconjugate triterpene, has the property to improve growth rate, immune regulation, antioxidant, anti-inflammatory. However, whether GL can attenuate myocardial I/R injury by modulating ferroptosis or other mechanisms are still unclear. In this study, SD rats underwent in vivo myocardial ischemia/reperfusion (I/R) surgery, while H9C2 cells were subjected to the hypoxia/reoxygenation (H/R) model for in vitro experiments. In addition, TAK-242, a TLR4-specific antagonist, and GL were also used to evaluate the effect and mechanisms of GL on the cardiac function and expression of ferroptosis-related gene and protein in vivo and vitro. The results show that GL decreased not only the expression of the inflammation-related factors (HMGB1, TNF-α, IL-6, IL-18 and IL-1β), but also reduced the number of TUNEL-positive cardiomyocytes, and mitigated pathological alterations in I/R injury. In addition, GL decreased the levels of MDA, promoted antioxidant capacity such as GSH, CAT, Cu/Zn-SOD, Mn-SOD, and SOD in vivo and vitro. More importantly, GL and TAK-242 regulate ferroptosis-related protein and gene expression in I/R and H/R model. Surprisingly, GL may ameliorate cardiomyocyte ferroptosis and ultimately improves cardiac function induced by H/R via the HMGB1-TLR4-GPX4 axis. Therefore, we have highlighted a novel mechanism by which GL regulates inflammation, oxidative stress, and ferroptosis via the HMGB1-TLR4-GPX4 pathway to prevent myocardial I/R injury. GL appears to be a potentially applicable drug for the treatment of myocardial I/R injury.

Promising Ursolic Acid as a Novel Antituberculosis Agent: Current Progress and Challenges.

Tuberculosis (TB) stands as the second most prevalent cause of global human mortality from infectious diseases. In 2022, the World Health Organization documented an estimated number of global TB cases reaching 7.5 million, which causes death for 1.13 million patients. The continuous growth of drug-resistant TB cases due to various mutations in the Mycobacterium tuberculosis (MTB) strain, raises the urgency of the exploration of novel anti-TB treatments. Ursolic acid (UA) is a natural pentacyclic triterpene found in various plants that has shown potential as a novel anti-TB agent. This review aims to provide an overview of the therapeutic prospects of UA against MTB, with a particular emphasis on in silico, in vitro, and in vivo studies. Various mechanisms of action of UA against MTB are briefly recapped from in silico studies, such as enoyl acyl carrier protein reductase inhibitors, FadA5 (Acetyl-CoA acetyltransferase) inhibitors, tuberculosinyl adenosine transferase inhibitors, and small heat shock protein 16.3 inhibitor. The potential of UA to overcome drug resistance and its synergistic effects with existing antituberculosis drugs are briefly explained from in vitro studies using a variety of methods, such as Microplate Alamar Blue Assay, Mycobacteria Growth Indicator Tube 960 and Resazurin Assays, morphological change evaluation using transmission electron microscopy, and in vivo studies using BALB/C infected with multi drug resistant clinical isolates. Besides its promising mechanism as an antituberculosis drug, its complex chemical composition, limited availability and supply, and lack of intellectual property are also reviewed as those are the most frequently occurring challenges that need to be addressed for the successful development of UA as novel anti-TB agent.

Ursolic Acid Inhibited Cholesterol Esterase and Pancreatic Lipase Activities and Decreased Micellar Cholesterol Solubility In Vitro

Ursolic acid (UA) is a natural triterpene carboxylic acid with an underlying anti-hyperlipidemia effect. This study examined the mechanism of interactions of UA with cholesterol esterase (CEase), pancreatic lipase (PL), and micellar cholesterol solubility in vitro. The half-maximal inhibitory concentration (IC50) of CEase, PL, and micellar cholesterol solubility was determined to be 0.07 ± 0.01 mg/mL, 1.81 ± 0.13 mg/mL, and 1.73 ± 0.08 mg/mL, respectively. Multispectral combination revealed that UA changed the secondary structure and quenched the intrinsic fluorescence by static quenching of the two enzymes. The interactions were exothermic reaction as determined by enthalpy. Furthermore, molecular docking confirmed that UA was bound to amino acids of two enzymes at active site through hydrophobic interaction and van der Waals forces. Molecular dynamics (MD) simulation found that CEase and PL rearranged with UA to form stable complexes. The strong inhibition effect of CEase and PL mediated by UA might provide additional insight into understanding the role of UA in the hypolipidemic effect.

Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.

Holothurian triterpene glycoside cucumarioside A2-2 induces macrophages activation and polarization in cancer immunotherapy

BackgroundDespite intensive developments of adoptive T cell and NK cell therapies, the efficacy against solid tumors remains elusive. Our study demonstrates that macrophage-based cell therapy could be a potent therapeutic option against solid tumors.MethodsTo this end, we determine the effect of a natural triterpene glycoside, cucumarioside A2-2 (CA2-2), on the polarization of mouse macrophages into the M1 phenotype, and explore the antitumor activity of the polarized macrophage. The polarization of CA2-2-pretreated macrophages was analyzed by flow cytometry and confocal imaging. The anti-cancer activity of CA2-2 macrophages was evaluated against 4T1 breast cancer cells and EAC cells in vitro and syngeneic mouse model in vivo.ResultsIncubation of murine macrophages with CA2-2 led to polarization into the M1 phenotype, and the CA2-2-pretreated macrophages could selectively target and kill various types of cancer in vitro. Notably, loading near-infrared (NIR) fluorochrome-labeled nanoparticles, MnMEIO-mPEG-CyTE777, into macrophages substantiated that M1 macrophages can target and penetrate tumor tissues in vivo efficiently.ConclusionIn this study, CA2-2-polarized M1 macrophages significantly attenuated tumor growth and prolonged mice survival in the syngeneic mouse models. Therefore, ex vivo CA2-2 activation of mouse macrophages can serve as a useful model for subsequent antitumor cellular immunotherapy developments.

Oxidative functionalization of triterpenes isolated from Euphorbia resinifera latex: Semisynthesis, ADME-Tox, molecular docking, and molecular dynamics simulations

Natural triterpenes isolated from Euphorbia resinifera latex, α-Euphol and α- Euphorbol, have been subjected to structural modification using oxidative agents such as chromic anhydride (CrO3) and sodium periodate in the presence of ruthenium trichloride NaIO4-(RuCl3, 3H2O) to obtain new triterpene derivatives with good yield. The semi-synthesized triterpenes (1–9) and (10–16) prepared from α-Euphol and α-Euphorbol have been tested in silico to predict and evaluate their antibacterial and insecticidal properties. Among the tested compounds, three of them (3, 15, and 16) were discarded after evaluating their drug-likeness and ADME-Tox profiles. Then, a molecular docking analysis was performed to predict which one of the studied compounds could inhibit MurE (PDB ID: 1E8C) and EcR (PDB ID: 1R20) proteins involved in antibacterial and insecticidal activities, respectively. Among the docked compounds, only compounds 8 and 9 showed better stability in the MurE and EcR receptor pocket than the Amoxicillin and 20-Hydroxyecdysone used as standards. After that, molecular dynamics simulation was performed to further investigate the stability of compound 9 in the binding pocket of both targeted receptors. Eventually, the outcomes of this study show that the new triterpene derivative 9 could be used as a promising candidate to develop new insecticides and antibacterial drugs.

Compounds with Anti-Alzheimer Activity Isolated for the First Time from Melaleuca leucodendron (L.) Leaves.

To discover a drug from natural triterpenes that has no side effects and is effective in treating Alzheimer's disease. We predict that the drug will be put on the market soon and achieve success. The methanolic extract of M. leucodendron leaves was fractionated and subjected to different chromatographic techniques to isolate two new triterpene glycosides alongside five known compounds kaempferol 3, quercetin 4, quercetin3-O-β-D-glucopyranoside 5, kaempferol3- O-β-D-glucopyranoside 6 and kaempferol3-O-α-L-rhamnoside 7. The structures of compounds 1 and 2 were elucidated by spectroscopic analysis and chemical means. Two new triterpene glycosides, 21-O-α-L-rhamnopyranosyl-olean-12-ene-3-O-[α-Lrhamnopyranosyl (1-4) β-D-galactopyranosyl (1-4) β-D-glucouronopyranoside]1 and 21-O-α-Lrhamnopyranosyl- olean-12-ene-3-O-[α-L-rhamnopyranosyl (1→4) β-D-galactopyra-nosyl (1→4) β-D-galactopyranoside] 2, were isolated for the first time from 70% aqueous methanolic extract (AME) of M. leucodendron leaves. The inhibitory activities of the said compounds toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were then assayed. Both compounds exhibited significant inhibitory activities toward the two enzymes, and evidence indicated that compound 2 was a more effective inhibitor than compound 1. Compounds 1 and 2 have a significant role in inhibiting the enzymes acetylcholinesterase and butyrylcholinesterase.

An analysis of the nutritional effects of Schisandra chinensis components based on mass spectrometry technology.

Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a Traditional Chinese medicinal herb that can be used both for medicinal purposes and as a food ingredient due to its beneficial properties, and it is enriched with a wide of natural plant nutrients, including flavonoids, phenolic acids, anthocyanins, lignans, triterpenes, organic acids, and sugars. At present, there is lack of comprehensive study or systemic characterization of nutritional and active ingredients of S. chinensis using innovative mass spectrometry techniques. The comprehensive review was conducted by searching the PubMed databases for relevant literature of various mass spectrometry techniques employed in the analysis of nutritional components in S. chinensis, as well as their main nutritional effects. The literature search covered the past 5 years until March 15, 2023. The potential nutritional effects of S. chinensis are discussed, including its ability to enhance immunity, function as an antioxidant, anti-allergen, antidepressant, and anti-anxiety agent, as well as its ability to act as a sedative-hypnotic and improve memory, cognitive function, and metabolic imbalances. Meanwhile, the use of advanced mass spectrometry detection technologies have the potential to enable the discovery of new nutritional components of S. chinensis, and to verify the effects of different extraction methods on these components. The contents of anthocyanins, lignans, organic acids, and polysaccharides, the main nutritional components in S. chinensis, are also closely associated to its quality. This review will provide guidelines for an in-depth study on the nutritional value of S. chinensis and for the development of healthy food products with effective components.

Pharmacological Potential of Betulin as a Multitarget Compound.

Betulin is a natural triterpene, usually from birch bark, known for its potential wound-healing properties. Despite having a wide range of pharmacological targets, no studies have proposed betulin as a multitarget compound. Betulin has protective effects against cardiovascular and liver diseases, cancer, diabetes, oxidative stress, and inflammation. It reduces postprandial hyperglycemia by inhibiting α-amylase and α-glucosidase activity, combats tumor cells by inducing apoptosis and inhibiting metastatic proteins, and modulates chronic inflammation by blocking the expression of proinflammatory cytokines via modulation of the NFκB and MAPKs pathways. Given its potential to influence diverse biological networks with high target specificity, it can be hypothesized that betulin may eventually become a new lead for drug development because it can modify a variety of pharmacological targets. The summarized research revealed that the diverse beneficial effects of betulin in various diseases can be attributed, at least in part, to its multitarget anti-inflammatory activity. This review focuses on the natural sources, pharmacokinetics, pharmacological activity of betulin, and the multi-target effects of betulin on signaling pathways such as MAPK, NF-κB, and Nrf2, which are important regulators of the response to oxidative stress and inflammation in the body.

Tripterine Inhibits Proliferation and Promotes Apoptosis of Keloid Fibroblasts by Targeting ROS/JNK Signaling.

Keloids are benign skin tumors characterized by excessive fibroblast proliferation and collagen deposition. The current treatment of keloids with hormone drug injection, surgical excision, radiotherapy, physical compression, laser therapy, cryotherapy often have unsatisfactory outcomes. The phytochemical compounds have shown great potential in treating keloids. Tripterine, a natural triterpene derived from the traditional Chinese medicine Thunder God Vine (Tripterygium wilfordii), was previously reported to exhibit an anti-scarring bioactivity in mouse embryonic fibroblast NIH/3T3 cells. Accordingly, our study was dedicated to explore its role in regulating the pathological phenotypes of keloid fibroblasts. Human keloid fibroblasts were treated with tripterine (0-10 μM) for 24 hours. Cell viability, proliferation, migration, apoptosis, and extracellular matrix (ECM) deposition were determined by CCK-8, EdU, wound healing, Transwell, flow cytometry, western blotting, and RT-qPCR assays. The effects of tripterine treatment on reactive oxygen species (ROS) generation and JNK activation in keloid fibroblasts were assessed by DCFH-DA staining and western blotting analysis. Tripterine at the concentrations higher than 4 μM attenuated the viability of human keloid fibroblasts in a dose-dependent manner. Treatment with tripterine (4, 6, and 8 μM) dose-dependently inhibited cell proliferation and migration, promoted cell apoptosis, reduced α-SMA, Col1, and Fn expression, induced ROS production, and enhanced JNK phosphorylation in keloid fibroblasts. Collectively, tripterine ameliorates the pathological characteristics of keloid fibroblasts that are associated with keloidformation and growth by inducing ROS generation and activating JNK signalingpathway.