BACKGROUND:Type-2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance (IR) and β-cell dysfunction. Nuciferine (NCF), derived from plants such as Nelumbo nucifera Gaertn., is an alkaloid with anti-obesity/T2DM effects. However, how NCF acts on hepatic lipid accumulation in T2DM treatment is not fully understood. PURPOSE:This study aims to investigate how NCF reverses hepatic steatosis and treats T2DM through the LKB1/AMPK/mTOR pathway. METHODS:High-fat diet-fed KK-Ay mice were used to establish an in vivo diabetic model. Insulin stimulation was used to establish hepatocyte models of IR. RESULTS:We found that NCF reduced body weight and blood glucose levels in diabetic mice. NCF also decreased the number of lipid droplets and triglyceride levels in liver. Furthermore, NCF reduced the overexpression of p-mTOR and the lipogenesis-related protein in liver of diabetic mice, while it elevated the protein levels of p-LKB1, p-AMPK, and p-ACC. In HepG2-IR cells, NCF significantly inhibited lipid accumulation via the LKB1/AMPK/mTOR pathway. When LKB1 or AMPK antagonists were used or LKB1 was knocked down by siRNA, the inhibitory effect of NCF on lipid accumulation was blocked. CONCLUSION:NCF inhibited hepatic lipid accumulation via the LKB1/AMPK/mTOR pathway, thereby contributing to the treatment of T2DM.

Oral colon-targeted drug delivery platforms are highly important for the treatment of ulcerative colitis (UC). In this study, an adhesive bilayer microgel (Cp@GTL) integrating time-lag positioning, interfacial mucoadhesive retention, and enzyme-triggered release was engineered for targeted colonic delivery. The adhesive bilayer microgels were loaded with costunolide (Cos), a natural sesquiterpene lactone exhibiting potent anti-inflammatory activity. The inner gel layer was constructed by crosslinking gelatin and low-methoxyl pectin through tannic acid and Ca2+ chelation, forming an interpenetrating network that confers colonic mucoadhesion and enzyme-responsive degradation properties. The outer shell was fabricated via polyelectrolyte complexation between anionic sodium alginate and cationic chitosan, endowing the system with resistance to gastric acid erosion through pH-responsive structural stabilization. In vitro release studies demonstrated that the microgels effectively retarded Cos release under simulated upper gastrointestinal conditions. Following oral administration in a dextran sulfate sodium (DSS)-induced UC mouse model, Cp@GTL significantly alleviated colitis symptoms, suppressed pro-inflammatory cytokine levels, and ameliorated colonic tissue damage. Furthermore, Cp@GTL exhibited prolonged colonic retention for up to 48 h with high drug accumulation at the target site, while also modulating gut microbiota composition, enhancing microbial diversity, and reducing the abundance of pathogenic bacteria, thereby synergistically contributing to the amelioration of DSS-induced colitis. This naturally derived bilayer microgel integrates time-programmed colonic positioning, interfacial mucoadhesive retention, and enzyme-triggered drug release, enabling coordinated anti-inflammatory intervention and gut microbiota regulation. It provides a promising strategy for enhancing the intestinal application of Cos in UC-associated inflammation and offers a versatile material platform and interfacial engineering approach for the targeted amelioration of intestinal inflammatory disorders.

Two new acylphloroglucinols, hengshanols F and G (1 and 2), were isolated from Hypericum hengshanense, together with nine known phloroglucinol derivatives: dauphinol F(3), 4-geranyl-2-(2 ' -methylpropionyl)-phloroglucinol (4), 1-[5,7-dihydroxy-2-methyl2-(4-methylpent-3-enyl)-chroman-8-yl]-2-methylpropan-1-one (5), 1-[5,7-dihydroxy-2- methyl-2-(4-methylpent-3-enyl)-chroman-8-yl]-2-methylbutan-1-one (6), empetriferdinan B(7), tomoeone B (8), uraloidin A (9), hyperbeanol P (10), ascyronone G (11). The structures of the two new acylphloroglucinols were determined by 1D NMR (H-1, C-13, DEPT), 2D NMR (HMBC, COSY, HSQC), HRMS and electronic circular dichroism (ECD). The structural elucidation revealed that all isolated compounds (1-11) are phloroglucinol derivatives. In cell viability assays, compounds 1, 5, 8, and 9 significantly reduced cell viability. whereas compound 6 promoted ATP production and enhanced mitochondrial activity

Ten previously undescribed flavonoids,seladoeflavones J-Q,C,and E(1-10),together with fifteen known biflavones(11-25),were isolated from the whole herbs of Selaginella doeder-leinii.The structures of the new compounds were elucidated using 1D and 2D nuclear magnet-ic resonance(NMR)spectroscopy and mass spectrometry(MS).By comparing experimental spectral data with NMR calculations,the structures of compounds 1-5,7,and 8 were as-signed.The absolute stereochemistries of compounds 5-10 were confirmed by comparing their circular dichroism(CD)spectra with reported data.Notably,the originally proposed structures of seladoeflavones C and E were revised and found to be identical to those of com-pounds 7 and 8,respectively.All isolated compounds were evaluated for cytotoxic activity against a panel of cancer cell lines.Most notably,2",3"-dihydroochnaflavone(14)and in-volvenflavone G(19)exhibited significant anti-proliferative and pro-apoptotic effects in laryngeal cancer cells(Hep-2 and FaDu).Mechanistic studies revealed that compound 14 in-duced apoptosis by suppressing the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway,whereas compound 19 downregulated endoplasmic reticulum(ER)stress pathways.These findings indicate that compounds 14 and 19 possess strong po-tential as anti-laryngeal cancer agents,providing robust evidence for the traditional use of S.doederleinii in the treatment of laryngeal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE:Swertia mussotii Franch, which Tibetan name is "Di-da" or "Zang Yin Chen," represents a significant Tibetan medicinal herb with an extensive background of use in clearing heat, detoxification, liver calming, promotion of bile secretion based on the Tibetan medicine theory. In Tibetan medicine, diabetes ("gcin snyi sa khu") is believed to result from imbalances among the three fundamental factors-Lung, Tripa, and Pekén-and is classified into subtypes with distinct clinical manifestations. S. mussotii is traditionally used to treat Tripa-type disorders and is incorporated into Tibetan formulations such as Tibetan Hypolipidemic Capsules and Shibawei Hezi Liniao Wan, as well as classical prescriptions including Shiwei Hezi Tangsan, for managing symptoms such as polyuria and hyperlipidemia. Despite its broad clinical use, there is limited understanding of the molecular mechanisms that contribute to its ability to hypoglycemic effects. AIM OF THE STUDY:This investigation pay attention to the hypoglycemic effects of Swertia mussotii Franch (SMF) and elucidate the regulatory mechanisms governing glucose metabolism and mitochondrial function in skeletal muscle. MATERIALS AND METHODS:The biological activities of SMF were tested using two experimental models following chemical profiling with UPLC-Q-TOF-MS: (i) in vitro experiments were performed in L6 myotubes at SMF concentrations of 20 and 40 μg/ml (n = 3). (ii) T2DM mice induced by STZ-HFD were used for in vivo studies, which received 100 or 200 mg/kg SMF (n = 3). Therapeutic efficacy was assessed using an integrated approach combining biochemical measurements, histological analyses, and molecular assays. RESULTS:Fifteen compounds were identified in SMF. In L6 myotubes, SMF significantly enhanced glucose uptake, improved mitochondrial function, and showed no cytotoxicity at the tested concentrations. In diabetic mice, SMF treatment conferred to decrease of body weight and fast blood glucose, alongside enhance insulin sensitivity and glucose tolerance. Additionally, this treatment restored mitochondrial functionality, maintained skeletal muscle fiber architecture, and promoted Glut4 expression. Mechanistic investigations indicated that these effects were associated with the activation of the Ampk/Pgc-1α signaling pathway. CONCLUSIONS:This study demonstrates that SMF exerts significant hypoglycemic effects by improving skeletal muscle glucose metabolism and mitochondrial function. By targeting skeletal muscle mitochondria and elucidating the involvement of Ampk/Pgc-1α signaling, this work supports the ethnopharmacological use of S. mussotii, which highlights the potential of its management for T2DM.

Artemisia argyi Lévl. et Van. (A. argyi) is a time-honored Traditional Chinese Medicine with a rich medicinal history. Its volatile oil possesses diverse pharmacological properties, including antioxidant, antiviral, and antitumor activities, among others. The quality of A. argyi volatile oil (AAVO) is influenced by its place of origin, which is highly correlated with its content of metabolites. In this study, AAVO was extracted according to the method of volatile oil determination (Method A) in the Pharmacopoeia of the People's Republic of China, and 21 batches of samples from the five origins of the leaves, namely, Qichun County, Hubei Province (HBQC); Nanyang City, Henan Province (HNNY); Anguo City, Hebei Province (HBAG); Tangyin County, Henan Province (HNTY); and Ningbo City, Zhejiang Province (ZJNB), were investigated using gas chromatography-mass spectrometry (GC-MS) and chemometric techniques. Initially, all samples were analyzed by GC-MS, and 80 metabolites were preliminarily identified by matching with the NIST Mass Spectrometry Search Program. These identifications were subsequently verified by comparing the calculated retention indices (RIs) of each compound with literature values. Six chemical markers were screened through principal component analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) analysis to effectively distinguish the five origins with significant geographical variability. Subsequently, the five metabolites were quantitatively analyzed by GC-MS to obtain more precise content information. This study is of great value for identifying the volatile oil of A. argyi from different origins, and also provides a reference for evaluating the quality of the volatile oil of A. argyi from different origins.

Seven new C21 steroidal glycosides, gymnetipregosides A - G (1-7), along with six known analogues, 12-O-cinnamoyl-20-O-nicotinoyl(20S)-pregn-6-ene-3β,5α,8β,12β,14β,17β,20-heptaol (8), 20-O-benzoyl-12-O-cinnamoyl-3β,5α,8β,12β,14β,17β,20-hepta-hydroxy-(20S)-pregn-6-ene (9), sylvepregoside A (10), gymnepregoside L (11), prosapogenin (12), and penupogenin-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside (13) were isolated from the ethyl acetate fraction of the roots and stems of Gymnema tingens. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and comparison with the reported data. All isolated compounds were evaluated for their effects on glucose uptake in L6 myotubes. At a concentration of 50 μM, compounds 1, 5, 7-9, 11, and 13 significantly increased glucose uptake by 1.39- to 1.89-fold. Subsequent cytotoxicity assays indicated that compounds 1, 5, 7, 8, 11, and 13 exhibited minimal cytotoxic effects. Further dose-response experiments demonstrated that compounds 8 and 11 showed the most potent activities at a concentration of 25 μM, increasing glucose uptake by 2.06- and 2.02-fold, respectively.

Background Quercetin, a flavonoid derived from astragalus and other medicinal plants, exhibits anti-cancer activity; however, its mechanisms in gastric cancer, especially regarding tumor immunity, remain incompletely understood. The aim of this study is to elucidate the mechanism of quercetin against gastric cancer. Methods Quercetin was evaluated in vitro for the effects on proliferation, apoptosis, cell cycle, mitochondrial potential, and morphology in MKN-45, AGS and normal GES-1 cells. Its efficacy and safety were assessed in vivo using a xenograft model. A “gastric cancer cells + T cells” co-culture system was established to examine quercetin's influence on T cell function. Target prediction employed network pharmacology, molecular docking, and molecular dynamics simulations, with validation via PD-L1 knockdown and PI3K overexpression rescue. Results Quercetin significantly inhibited MKN-45 proliferation, induced G0/G1 arrest, and promoted apoptosis, accompanied by mitochondrial damage, loss of membrane potential, downregulation of BCL-2, and upregulation of BAX, CytC, cleaved Caspase-9, and cleaved Caspase-3. In vivo, quercetin reduced tumor growth, decreased Ki-67, increased tumor apoptosis and peripheral CD8+ T cells, with no apparent organ toxicity. In co-culture, quercetin enhanced CD8+ T cell cytotoxicity, increasing granzyme B, perforin, IL-2, and IFN-γ. Mechanistically, quercetin bound PD-L1, reduced its protein expression without affecting mRNA, and suppressed the PI3K-AKT signaling pathway. Conclusion Quercetin exhibited a dual mechanism: it directly suppressed gastric cancer cell proliferation and induced mitochondria-mediated apoptosis, while also enhancing CD8+ T cell cytotoxicity. Its anti-cancer mechanism involved modulation of PD-L1 protein expression and suppression of the PI3K-AKT signaling pathway. These findings supported the feasibility of quercetin as a potential therapeutic candidate for gastric cancer.

Ethnopharmacological relevance: Hypericum scabrum L. is a traditional medicinal plant used in Kazakh medicine for clearing heat, promoting blood circulation, and resolving stasis. These traditional actions are considered relevant to the management of metabolic disorders characterized by “heat” and “stasis,” which conceptually overlap with the pathogenesis of type 2 diabetes mellitus (T2DM) and its associated lipid metabolic disturbances. Despite its longstanding ethnomedicinal use, the anti-diabetic activity of H. scabrum and its underlying pharmacological mechanisms have not been systematically investigated.Aim of the study: To evaluate the anti‑diabetic effects of the ethyl acetate fraction of H. scabrum (HS) and elucidate its role in hepatic glucose/lipid metabolism and mitochondrial function via the LKB1/AMPKα/ACC pathway.Materials and methods: The chemical composition of HS was characterized by UPLC-Q-TOF-MS, and its potential targets and pathways were predicted using network pharmacology. The anti-diabetic effects of HS were evaluated in high-fat diet/streptozotocin (HFD/STZ)-induced T2DM mice treated with HS (100 or 200 mg/kg) for 8 weeks and in oleic acid-induced insulin-resistant HepG2 cells treated with HS (10 or 20 μg/mL).Results: Sixteen compounds were identified in HS, mainly polyisoprenylated acylphloroglucinols. Network pharmacology analysis suggested AMPK signaling as a key pathway. HS significantly reduced fasting blood glucose, improved insulin sensitivity and dyslipidemia, alleviated hepatic steatosis, and enhanced mitochondrial oxidative phosphorylation, as indicated by increased activities of mitochondrial respiratory chain complexes I, II, IV, and V. HS also increased the phosphorylation levels of LKB1, AMPKα, and ACC in vivo and in vitro.Conclusion: HS exerts anti-diabetic effects by activating the LKB1/AMPKα/ACC pathway, thereby improving hepatic lipid metabolism and mitochondrial function. These findings provide pharmacological evidence supporting the traditional Kazakh medicinal use of H. scabrum in the management of T2DM-related metabolic disorders.​

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ.

Three new compounds, kouytchin A (1), kouytchin B (2), and 2,4,5,10-tetramethoxydibenzo[1,4]dioxin (3), along with nine known compounds (4-12), were isolated and purified from the ethyl acetate extract of Hypericum kouytchense H L & eacute;v. The known compounds were identified as uraloidin A (4), uralione D (5), biyoulactones B (6), xanthone derivatives (7-11), and 3-hydroxy-1,4,7-trimethoxydibenzofuran (12). The structures of new compounds were elucidated based on comprehensive spectroscopic analysis, including 1D NMR (1H, 13C and DEPT), 2D NMR (HMBC, COSY and HSQC), HRMS, and electronic circular dichroism (ECD). Furthermore, compounds 4 and 5 exhibited potent cytotoxic activity against the gastric cancer cell MKN-45, with half-maximal inhibitory concentration (IC50) values of 16.00 +/- 0.86 mu M and 18.47 +/- 0.95 mu M, respectively. These findings enrich the phytochemical knowledge of H. kouytchense and highlight the potential of its constituents as leads for anticancer drug discovery.

Eight previously undescribed compounds, davidinins B-G (1-4, 5a, 5b, 6a and 6b), including two sets of enantiomeric pairs (5a/5b and 6a/6b) together with six known compounds, were isolated from the ethyl acetate fractions of the roots of Sophora davidii (Franch.) Skeels. Using chiral HPLC, the enantiomers (+)-(3R,4R)-davidinin F (5a), (-)-(3S,4S)-davidinin F (5b), (+)-(R)-davidinin G (6a), and (-)-(S)-davidinin G (6b) were successfully separated and obtained. Their planer structures were established through analysis of 1D and 2D NMR and HRESIMS data. The absolute configurations of the previously undescribed compounds were mainly determined by NMR calculation and electronic circular dichroism (ECD) calculation. At a concentration of 20 mu g/mL, compounds 1-4, 5a, 5b, 6a, 6b, and 7-9 modulated GLUT4 translocation to 1.15-2.47-fold of the control; among them, compound 4 exhibited the strongest increase.

Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8-16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 mu M) and 16 (123.15 mu M) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical applications.

Ethnopharmacological relevance Caragana jubata (Pall.) Poir., a traditional Tibetan medicinal plant in China, is renowned in Tibetan medicine for its hypoglycemic properties and long-standing use in treating diabetes. Despite its extensive clinical use, the mechanisms underlying its blood sugar-lowering effects still need to be explored. Our investigation contributes a new understanding of the hypoglycemic mechanism of C. jubata, validating its traditional medicinal application by demonstrating its ability to increase GLUT4 expression and glucose uptake, crucial elements in treating type 2 diabetes mellitus (T2DM). Aim of the study This study investigated the potential anti-diabetic effects of C. jubata ethanol extract (CJEE) by upregulating GLUT4 expression and promoting its integration into the plasma membrane in L6 skeletal muscle cells and diabetic mice. Additionally, the research aimed to uncover the mechanisms involved, particularly focusing on the involvement of the PKC signaling pathway and Ca2⁺ release. Materials and methods The chemical composition of CJEE was evaluated using UPLC-Q-TOF/MS. Glucose uptake, GLUT4 expression, and plasma membrane fusion in L6 cells were assessed through a glucose oxidase kit, Western blotting, and laser confocal microscopy, respectively. The modulation of GLUT4 by Akt, AMPK, and PKC signaling pathways was investigated utilizing specific inhibitors. The impact of CJEE on intracellular Ca2⁺ concentration was determined with Fluo-4 dye. Additionally, an in vivo study was conducted on high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice to evaluate the effects of CJEE on blood glucose levels, insulin resistance, lipid metabolism, and pancreatic function. Results Chemical analysis of CJEE revealed 18 major constituents, primarily flavonoids. In L6 cells, CJEE was found to significantly enhance glucose uptake, increase GLUT4 expression, and facilitate its fusion with the plasma membrane. The study illustrated that CJEE predominantly activates the PKC pathway, with minimal involvement of the Akt pathway, emphasizing the critical role of Ca2⁺ release in GLUT4 regulation. Diabetic mice treated with CJEE exhibited decreased fasting blood glucose levels, enhanced oral glucose tolerance, reduced insulin resistance, and ameliorated lipid metabolism disorders. Additionally, CJEE elevated GLUT4 expression in insulin-sensitive tissues and alleviated pancreatic and hepatic lesions. Conclusions Our results demonstrated that the activation of the PKC pathway and release of Ca2⁺ by CJEE induce GLUT4 expression, promoting its fusion with the plasma membrane. Consequently, this process boosts glucose uptake and enhances insulin sensitivity, underscoring CJEE as a promising option for managing T2DM.

Diabetic kidney disease (DKD) is one of the complications of diabetes mellitus, which triggers kidney fibrosis and eventually develops into end-stage renal disease. Nuciferine (NF) is one of the most important functional components in lotus leaves (LL), but its role and mechanism for the treatment of DKD are unclear. A high-fat-diet (HFD)-induced DKD model in KK-AY mice was established in this study. NF treatment significantly improved blood glucose and blood biochemical indices in DKD mice. Furthermore, NF reduced the levels of mALB, UCRE, Scr, and BUN in mice urine. Further, the extent of renal lesions in the mice in this study was at stage IV according to the Mogensen staging method. NF treatment was effective in ameliorating renal injury during this period. Concurrently, the protein levels of FN, N-cadherin, TGFβ, p-Smad3, p-PI3K, p-AKT, p-mTOR, and p62 were decreased. In contrast, the level of expression of Beclin-1 was increased. In the high glucose-exposed HK-2 cell model, the expression of p-PI3K, p-AKT, and p-mTOR was all downregulated, and autophagy proteins were increased after NF intervention. In addition, HK-2 cells were treated with high glucose in combination with Wortmannin and 3-MA, respectively. The results demonstrated that NF inhibited the expression of TGFβ and p-Smad3 by regulating autophagy through the PI3K-AKT-mTOR pathway, thereby ameliorating renal fibrosis at stage IV in mice. Therefore, LL can be used as a dietary component for the prevention of renal fibrosis in DKD patients.

A phytochemical investigation on the ethyl acetate fraction of Gymnema sylvestre led to the production of nine previously undescribed C21 steroidal glycosides sylvepregosides F-N (1-9), as well as ten known analogues, prosapogenin (10), 20-O-benzoyl-12-O-cinnamoyl-3β,5α,8β,12β,14β,17β,20-heptahydroxy-(20S)-pregn-6-ene (11), 12-O-cinnamoyl-3β,5α,8β,12β,14β,17β,20-heptahydroxy- (20S)-pregn-6-ene (12), stephanoside K (13), gymnepregoside C (14), gymnepregoside D (15), stephanoside O (16), isokidjoladinin (17), gymsyloside D (18) and gymsyloside C (19). The structures of these isolated compounds were elucidated based on extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectrometry data. The biological activities screening demonstrated that compounds 1, 3-6, 8-10, 12-14, 17, and 18 promoted glucose uptake by the range of 1.06-1.97 folds. In addition, compounds 3-6, 8, 13, 14, and 19 could promote GLUT-4 translocation to the plasma membrane in L6 cells.

Ten previously undescribed pyrrolidine alkaloids, namely penicipyrrolidines O–X (1–10), were isolated from the mangrove-derived fungus Penicillium sp. DM27, along with five known compounds (11–15). Their structures were determined by comprehensive analysis of HRESIMS and NMR spectroscopic data, and the absolute configurations were established based on biosynthetic considerations and TDDFT-ECD calculations. All isolates were evaluated for their glucose uptake capacity. Notably, penicipyrrolidine P (2) significantly enhanced cellular glucose uptake in L6 myotubes by 3.83-fold, demonstrating activity comparable to that of metformin, whereas penicipyrrolidines Q and R (3 and 4) showed relatively weaker effects.

Ethnopharmacological relevance Panax notoginseng (Burkill) F.H. Chen, documented in the Compendium of Materia Medica, promotes blood circulation and removes stasis. Despite extensive research, the above-ground parts (stems and leaves) remain underutilized. The synergistic mechanism of the effects of hawthorn (Crataegus pinnatifida) juice (SZ) on Panax notoginseng stem-leaf extract (SQ) to regulate sugar and lipid metabolism has not been reported. Aim of the study To elucidate SZ's effects on SQ saponins and their synergistic mechanisms in glucose/lipid metabolism. Materials and Methods The optimum technological parameters of SSZ were determined using single-factor and orthogonal tests, and the effectiveness of SSZ in regulating glucose and lipid metabolism was investigated using a high-fat and high-sugar model. The main saponins were characterized using LC-MS/MS, the synergistic mechanism of rare saponins was analyzed using network pharmacology and molecular docking, and the Rb3 transformation pathway was analyzed using transformation kinetics. Results The results showed that SSZ could enhance the synergistic effect, alleviate liver injury, significantly improve the metabolic parameters of glucose and lipids, and adjust blood viscosity. Mechanistically, maslinic acid in SZ hydrolyzed protopanaxadiol saponins into active rare ginsenosides (S/R-Rg3, Rg5, and Rk1) through selective glycoside cleavage. Conclusion This study solved the problems of the limited curative effect of monotherapy and difficulty in obtaining rare saponins with high activity, provided innovative strategies for functional food development, promoted the efficient utilization of aboveground resources of Panax notoginseng, and was very important for solving the global disorder of glucose and lipid metabolism and promoting the application of natural products.

Extracellular matrix (ECM) and integrins are important biological macromolecules. ECM especially collagen IV (COLIV) deposition modulates the integrin-FAK signaling pathway involved in adipogenesis and is strongly associated with insulin resistance. Type 2 diabetes mellitus (T2DM) mice were given swertiamarin (STM) by intragastric administration. STM reduced body weight, blood glucose, and lipid levels and enhanced insulin sensitivity in diabetic mice. The lipid accumulation in liver, gastrocnemius muscle, and inguinal subcutaneous white adipose tissue (igSWAT) were significantly reduced by STM. Bioinformatics analysis revealed a connection between ECM, ITGB1/FAK, and PI3K/Akt signaling pathways. STM downregulated the adipogenesis, IRβ expression, COLIV deposition, ITGB1/FAK, and PI3K/Akt signaling pathways in igSWAT of diabetic mice. In vitro, STM inhibited the glucose uptake and differentiation of adipocytes, and downregulated adipogenesis-related gene and protein expression. STM is bound to ITGB1 and downregulated COLIV deposition, ITGB1/FAK, and PI3K/Akt signaling pathways. When we overexpressed FAK, the effects of STM on downstream PI3K/Akt signaling pathway and adipogenesis were attenuated. In conclusion, STM reduced COLIV deposition and binding with ITGB1 to downregulate ITGB1/FAK signaling pathway, further the downstream PI3K/Akt signaling pathway was inhibited to reduce adipogenesis and ameliorated T2DM. Thus, these signals may be a novel mechanism of STM in treating T2DM.