Search Results (133)

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Background: Reducing postprandial blood glucose (PBG) is a crucial strategy for treating diabetes and minimizing the risk of complications. Developing efficient and safe α-glycosidase inhibitors from natural products to lower PBG has attracted much attention. Silphium perfoliatum L. (SP), a traditional herbal medicine of North American Indigenous tribes, has efficacy of treating metabolic diseases, but its hypoglycemic activity and bioactive components have not been fully studied. Methods: In vitro α-glucosidase inhibition and in vivo sucrose/maltose/starch tolerance assays were performed to assess the hypoglycemic effects of SP extracts, and UPLC-Triple-TOF-MS/MS analysis was used to tentatively identify its chemical structure composition. In vitro enzyme inhibition and molecular docking were used to verify the effective ingredients. Results: In vitro hypoglycemic activities of four extracts of SP (SP-10/SP-40/SP-60/SP-C) showed that SP-10 exhibited strong α-glucosidase (sucrase and maltase) inhibitory effects with IC₅₀ of 67.81 μg/mL and 62.99 μg/mL, respectively. Carbohydrate tolerance assays demonstrated that SP-10 could significantly reduce the PBG levels of diabetic mice, with a significant hypoglycemic effect at a dosage of 20 mg/kg. A total of 26 constituents, including 11 caffeoylquinic acids (CQAs) and 15 flavonol glycosides, were tentatively identified by mainly analyzing secondary MS fragmentation. Moreover, three CQAs rich in SP-10, namely chlorogenic acid (CGA), neochlorogenic acid (NCGA), and cryptochlorogenic acid (CCGA), may be the main hypoglycemic substances, as evidenced by their inhibitory effects on sucrase and maltase. Conclusions: The α-glucosidase inhibitory effects of SP extract both in vitro and in vivo and its active ingredients were systematically studied for the first time. Results indicated that SP extract, rich in CQAs, had significant hypoglycemic activity, supporting the considerable potential of SP as hypoglycemic functional food or cost-effective therapeutic agents for diabetes treatment. Full article

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE’s antioxidant activity was evaluated in vitro through DPPH, H₂O₂, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride–Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment. Full article

Polycystic ovary syndrome (PCOS) and diabetes mellitus (DM) are prevalent endocrine disorders with overlapping pathophysiological mechanisms. Type 2 diabetes mellitus (T2DM) is commonly associated with PCOS, with both conditions strongly linked to insulin resistance (IR), while recent studies have also reported an increased prevalence of PCOS among women with type 1 diabetes mellitus (T1DM). This study evaluated the potential of Lythrum salicaria L. ethanol extract (LSEE) to mitigate oxidative stress (OS), inflammation, and metabolic and hormonal imbalances in separate experimental models of Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. LSEE underwent phytochemical analysis to quantify total phenolic and flavonoid content and HPLC-MS for polyphenols identification. In vitro, antioxidant capacity was investigated through FRAP, DPPH, NO, and H₂O₂ scavenging assays. Subsequently, in vivo, studies utilized STZ-induced DM and LET-induced PCOS rat models, with 10-day treatments of LSEE, metformin, or trolox (TX) administered by gavage. Dysregulation of hormonal profiles, ultrasound, and histological examinations confirmed PCOS development. At the end of the treatment period, serum samples were collected to assess OS markers (TOS, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, TAR, SH) in both models. Inflammatory markers were also measured (IL-1β, NF-κB, IL-18, and Gasdermin D in DM and IL-1β, NF-κB, IL-18, and IL-10 in PCOS). Additionally, metabolic markers (glucose, lipids, TG-glucose index, liver enzymes) were assessed in DM rats, and hormones (LH, FSH, estrogen, testosterone, insulin, HOMA-IR) were determined in PCOS rats. LSEE demonstrated a high polyphenolic content and notable in vitro antioxidant activity. In vivo, it effectively reduced OS by lowering oxidant levels and enhancing antioxidant defenses, reduced inflammatory markers and blood glucose levels, and improved lipid profiles along with the TyG index and liver injury markers in diabetic rats. In PCOS rats, LSEE lowered the total oxidants, increased antioxidants, reduced LH, FSH, testosterone, and insulin, and increased estrogen levels. The effects exhibited a dose-dependent pattern, with higher doses producing more pronounced benefits comparable to those observed with metformin and TX. In conclusion, LSEE may be a promising complementary treatment for DM and PCOS. Full article

Traditional Chinese medicine has long acknowledged the therapeutic potential of Tetradium ruticarpum (A.Juss.) T.G.Hartley together with Coptis chinensis Franch in managing metabolic disorders. However, their combined anti-obesity effects and the underlying mechanisms remain poorly characterized. This study investigates the synergistic anti-obesity effects and mechanisms of a combined berberine and evodiamine treatment (BBE) in high-fat diet (HFD)-induced C57BL/6J mice and 3T3-L1 cells. In vitro, cell viability was evaluated using the Cell Counting Kit-8 (CCK-8), while lipid accumulation was assessed through Oil Red O staining and triglyceride content determination. Molecular docking simulations performed with AutoDockTools 1.5.6 software Vina predicted interactions between BBE and key proteins. The analysis of genes and proteins involved in browning and thermogenesis was conducted using quantitative reverse transcription polymerase chain reaction and Western blotting. In vivo, HFD-induced mice were assessed for serum lipids profiles, glucose, insulin, adipocytokines, fat tissue morphology (Hematoxylin and eosin staining), mitochondrial activity (flow cytometry), and protein expression (immunofluorescence). Molecular docking analysis revealed strong binding affinities between BBE and key target proteins, including UCP1, PGC-1α, PRDM16, CIDEA, FGF21, and FGFR1c. BBE significantly reduced lipid accumulation in 3T3-L1 cells, upregulated the mRNA expression of Prdm16, Cidea, Ucp1, and Dio2, elevated UCP1 and PGC-1α protein levels, and activated the FGF21/PGC-1α signaling pathway. In HFD-induced mice, BBE administration led to reduced body weight, smaller adipocyte size, increased adipocyte number, and alleviated hepatic steatosis. Furthermore, it lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and levels of triglycerides (TG), while simultaneously increasing concentrations of high-density lipoprotein cholesterol (HDL-C). BBE also improved glucose tolerance, reduced fasting insulin levels, and modulated adipocytokine levels (reduced leptin, increased adiponectin), while promoting browning gene and protein expression. Overall, the combination of berberine and evodiamine mitigates obesity by enhancing browning and activating the FGF21/PGC-1α signaling pathway. Full article

Matrine, a quinoline alkaloid, possesses lipid-regulating effects, but the underlying mechanisms are rarely characterized in vivo. With a fat-accumulating Caenorhabditis elegans model, we show that matrine reduces the fat content and the DHS-3::GFP-labeled lipid droplets in high-glucose-diet N2 and transgenic LIU1 nematodes, respectively. Based on RNA-seq, this study demonstrates that a loss of AAK-2 function suppresses the fat-lowering effects of matrine, and the hyperactivated AAK-2 strain has a relatively lower fat content than N2. The involvement of NHR-49 in matrine’s fat-lowering effects further suggests that matrine impacts fat breakdown and storage via the AAK-2/NHR-49-governed pathway. Using the transgenic SJ4143 (ges-1::GFP(mit)) and VS10 (vha-6p::mRFP-PTS1), we show that matrine activates the AAK-2/NHR-49 pathway, coupling the alteration of mitochondrial and peroxisomal functions. Studies of aak-2 and nhr-49 mutants reveal that AAK-2 and NHR-49 modulate lipid metabolic homeostasis; meanwhile, matrine increases physical fitness and lifespan through activating the AAK-2/NHR-49 pathway in high-glucose-diet nematodes. Surprisingly, we found that β-amyloid (Aβ) induces lipid metabolic disorder in an Alzheimer’s disease (AD) C. elegans model, but matrine not only reduces Aβ aggregation but also alleviates Aβ-mediated lipid metabolic disorder. Our data suggest that matrine has promise as a fat-lowering agent, and also offer new insights into its therapeutic potential for AD. Full article

Diabetes mellitus is a chronic, degenerative, and multifactorial disease characterized by hyperglycemia, and at least 537 million people suffered from diabetes in 2021. Agave durangensis Gentry, a species of agave native to the state of Durango, reports phenolic compounds, flavonols, flavonoids, and saponins and could be an alternative for the treatment of diabetes. The aim of this work was to identify the compounds in the leaves of Agave durangensis Gentry and their potential activity in diabetes. The leaf extract of Agave durangensis Gentry (EAD) was characterized by ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), and different families of bioactive compounds were quantified by analytical methods. Probable pharmacological targets were identified in silico, and the inhibition of dipeptidyl peptidase-4 (DPP4) was validated in vitro. A model of hyperglycemia was established with streptozotocin in male Wistar rats, and we administered EAD intragastrically at a dose of 300 mg/kg, as well as combinations of the extract with metformin and sitagliptin over 30 days. Biochemical and histological parameters were analyzed. We identified thirty-six major compounds, where triterpenes represented 30% of the extract. Molecular docking showed that the extract could interact with α-glucosidases and DPP4 since a large number of compounds in the extract have a Δ G lower than that reported for the controls, and DPP4 inhibition was confirmed by in vitro assays. In vivo assays demonstrated that the administration of the extract was able to significantly decrease glucose levels by 56.75% and glycosylated hemoglobin by 52.28%, which is higher than that reported for sitagliptin with a decrease of 35.22%. In addition, the extract decreased triglycerides by 59.28% and very-low-density lipoprotein (VLDL) cholesterol by 60.27%, and when administered in combination with metformin, it decreased them more than when metformin was administered alone. For all the above reasons, Agave durangensis Gentry extract could be used for the development of phytomedicine for the treatment of diabetes. Full article

Background/Objectives: This study explores the bioactive potential of Bovistella utriformis biomass and its polysaccharides (PsBu) through comprehensive biochemical and bioactivity analyses, focusing on their antioxidant, cytotoxic, and antihyperglycemic properties. Methods: Elemental analysis determined the biomass’s chemical composition. Antioxidant activity was assessed using ABTS and DPPH assays. Monosaccharide composition was analyzed via gas chromatography-mass spectrometry (GC-MS). In vitro cytotoxicity assays were conducted on cancer and normal cell lines to determine IC₅₀ values and selectivity indices (SI). Zebrafish embryo toxicity was evaluated for teratogenic effects, and an in vivo antihyperglycemic study was performed in diabetic rat models. Results: The biomass exhibited high carbon content (around 41%) and nitrogen levels, with a balanced C/N ratio nearing 5. Protein content exceeded 50%, alongside significant carbohydrate, fiber, and ash levels. Antioxidant assays revealed inhibition rates of approximately 89% (ABTS) and 64% (DPPH). GC-MS analysis identified glucose as the predominant sugar (>80%), followed by galactose and mannose. Additionally, HPLC detected a photoprotective compound, potentially a mycosporin-like amino acid. Cytotoxicity assays demonstrated PsBu’s selective activity against colon, lung, and melanoma cancer cell lines (IC₅₀: 100–500 µg·mL⁻¹), while effects on normal cell lines were lower (IC₅₀ > 1300 µg·mL⁻¹ for HaCaT, >2500 µg·mL⁻¹ for HGF-1), with SI values approaching 27, supporting PsBu’s potential as a targeted anticancer agent. Zebrafish embryo assays yielded LC₅₀ values ranging from 1.4 to 1.8 mg·mL⁻¹. In vivo, PsBu reduced fasting blood glucose levels in hyperglycemic rats (approximately 210 mg·dL⁻¹ vs. 230 mg·dL⁻¹ in controls) and preserved pancreatic β-cell integrity (around 80% vs. 65% in controls). Conclusions: These findings suggest that B. utriformis biomass and PsBu exhibit strong antioxidant activity, selective cytotoxicity against cancer cells, and antihyperglycemic potential, making them promising candidates for further biomedical applications. Full article

Background: Advanced glycation end-products (AGEs) are linked to the development of oxidative stress, insulin resistance, and impaired insulin secretion. Adverse early life conditions, such as exposure to AGEs and their precursors, may lead offspring to the development of metabolic dysfunction in adulthood. Nonetheless, the early impact in offspring metabolism by maternal intake of AGEs precursors during lactation is not known. Objective: Investigate early life metabolism of the offspring whose breastfeeding dams were orally exposed to AGEs precursor. Methods: Breastfeeding Wistar rats were daily treated with the glycation precursor methylglyoxal (MG—60 mg/kg of bodyweight) by gavage or saline 0.9% control (CO) until weaning. In vivo glycemic homeostasis in male offspring was assessed, followed by euthanasia for tissue sample collection for ex vivo assessments. Results: At weaning, MG offspring presented decreased bodyweight (p < 0.05), perigonadal (p < 0.01) and retroperitoneal (p < 0.01) fat. MG offspring presented decreased glucose tolerance (p < 0.05), lower basal insulinemia (p < 0.001), reduced high-glucose static insulin secretion (p < 0.05), and reduced pancreatic islet area (p < 0.05). Accordingly, MG offspring pancreas showed lower GSH and SOD activity (p < 0.05; p < 0.001, respectively) and increased MPO (p < 0.05) activity. Conclusions: The consumption of AGE precursors by breastfeeding dams impaired offspring pancreatic function and glycemic homeostasis early in life. Full article

Background: An over-the-counter vasoconstrictive nasal solution with oxymetazoline (NS-OXY, 0.05%) has the potential to be used as a dental pulpal hemostatic medicament. A molecular engineering approach examined NS-OXY and its molecular constituent’s antimicrobial and blood biomass removal efficacy. Methods: An ex vivo cavity model was developed where standardized prepared teeth were exposed overnight to a model dentinal caries pathogen, S. mutans, and then exposed to sheep’s blood for 10 min, which simulated a pulpal exposure. Cavity preparations were rinsed with OXY (0.05%), benzalkonium chloride (BKC-0.025%), NS-OXY (with OXY-0.05% and BKC), ferric sulfate (20%;ViscoStat, FS), and distilled water (DI). For examining the bactericidal effect of NS-OXY, a disk diffusion antimicrobial assay was used where S. mutans was grown (20 h) on brain heart infusion (BHI) w/0.5% glucose agar plates and exposed to the treatment groups. Results: NS-OXY-treated samples had a lower residual bacterial or blood biomass than FS (p = 0.003). The diffusion test showed that NS-OXY, BKC, and FS had zones of inhibition greater than 10 mm, with NS-OXY having higher activity against S. mutans than FS (p = 0.0002), but lower than BKC (p = 0.0082). Conclusions: NS-OXY may be considered as a dental hemostatic agent after traumatic and carious pulpal exposure owing to NS-OXY’s antimicrobial and vasoconstrictive properties. Full article

Lychee peel generated during the industrial processing of lychee fruit are currently disposed of as agricultural waste. This study investigates the primary components of lychee peel extract (LPE) and the regulatory mechanisms of LPE on reducing uric acid (UA). Mice were injected with hypoxanthine and potassium oxonate to induce hyperuricemia and concurrently orally administered LPE. The analysis of the LPE composition reveals a predominance of polyphenolic compounds, including (-)-epicatechin, (-)-epigallocatechin, and procyanidin A2. In vitro tests have demonstrated that the LPE significantly inhibits the activity of xanthine oxidase (XOD). In vivo studies showed that LPE can reduce UA levels in hyperuricemia mice. Further mechanistic insights indicate that LPE inhibits hepatic XOD activity, thereby reducing UA synthesis within the organism. It also decreases the protein expression of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9), which leads to diminished UA reabsorption and increased excretion of UA. Additionally, LPE enhances the activity of superoxide dismutase (SOD) while simultaneously reducing malondialdehyde (MDA) contents, thereby improving antioxidant capacity in mice. Our findings indicate that LPE not only inhibits the production of UA but also promotes its elimination, positioning it as a promising candidate for UA-lowering agents. Full article

Asthma is a chronic inflammatory respiratory disease that affects millions globally and poses a serious public health challenge. Current therapeutic strategies, including corticosteroids, are constrained by variable patient responses and adverse effects. In this study, a polyphenolic extract derived from the Tibetan medicinal plant Spenceria ramalana Trimen (SRT) was employed and shown to improve experimentally (ovalbumin + cigarette smoke, OVA + CS) induced asthma in rats. Initially, the potential therapeutic mechanism of the polyphenolic components in SRT on OVA + CS-induced asthma was predicated by network pharmacology analysis. Subsequently, in vivo experiments identified that SRT polyphenols exhibit significant anti-asthmatic activities, primarily mediated by lowering inflammatory cell counts such as the WBC (white blood cell), eosinophils, and neutrophils, decreasing the expression of inflammatory cytokines (IL-4, IL-5, IL-13, and TNF-α), alleviating lung histological damage (reduced inflammation, collagen deposition, and mucus secretion), and enhancing the epithelial barrier integrity (upregulation of ZO-1, occludin, and claudin-1). Additionally, SRT polyphenols downregulated the PI3K/Akt (Phosphoinositide 3-kinase/protein kinase B) signaling pathway, improved gut microbiota disruption, and regulated fecal metabolites (glucose-6-glutamate, PS (16:0/0:0), 8-aminocaprylic acid, galactonic acid, Ascr#10, 2,3,4,5,6,7-hexahydroxyheptanoic acid, phosphodimethylethanolamine, muramic acid, 9-oxohexadeca-10e-enoic acid, and sedoheptulose) in asthmatic rats. In conclusion, SRT polyphenols exerted multifaceted protective effects against OVA + CS-induced asthma in rats, highlighting their potential value in preventing asthma via the PI3K/Akt signaling pathway. Full article

Eryptotic erythrocytes are prone to adhere to the vascular endothelium, provoking atherosclerosis. As statins do not prevent eryptosis compounds with anti-eryptotic effects could help treated hypercholesterolemic subjects in decreasing cardiovascular disease risk. Plant sterols (PSs) have shown this anti-eryptotic effect ex vivo, along with their cholesterol-lowering activity. A parallel double-blind placebo-controlled randomized trial was conducted using a PS-food supplement (2 g of PS/day) (case, n = 13) or a placebo supplement (control, n = 13) in statin-treated hypercholesterolemic subjects. Blood samples were extracted before (T0) and after (T1) a 6-week treatment, and erythrocytes were isolated for biochemical determination, phosphatidylserine externalization (EPHS), cell size and reduced glutathione (GSH) analyses, and endothelium adhesion evaluation. A reduction in glucose (4.3%) and LDL cholesterol (9.2%) was observed only in the control group, whereas in the case group, an increase in ApoA1 (6.4%) was observed. Neither EPHS, cell size nor GSH were modified by the treatment with any of the supplements, whilst endothelium adhesion was reduced (55.1%) only in the case group. These results suggest that the PS supplement may improve some cardiovascular health parameters in the target population even though eryptosis status is not modified by this treatment. Full article

Objectives: Traditional Chinese Medicine (TCM) is recognized for its complex composition and multiple therapeutic targets. However, current pharmacological research often concentrates on extracts or individual components. The former approach faces numerous challenges, whereas the latter oversimplifies and disregards the synergistic effects among TCM components. This study aims to investigate the scientific validity of focusing on the active constituent in TCM efficacy research, using Pueraria lobata (P. lobata) as a case study. Methods: Through spectrum-effect correlation analysis, network pharmacology, and molecular docking, five active ingredients of P. lobata were identified: puerarin, formononetin, tuberosin, 4′,7-dihdroxy-3′-methoxyisoflavone, and Daidzein-4,7-diglucoside. These ingredients were combined to form an active constituent, which was subsequently tested in vitro and in vivo. Results: In in vitro, the active constituent exhibited superior effects in enhancing glucose consumption and glycogen synthesis compared to both the P. lobata extract and individual components. In vivo experiments demonstrated that medium and high doses of the active constituent were significantly more effective than P. lobata extract, with effects comparable to those of metformin in reducing blood sugar levels. Conclusions: The active constituent effectively improves T2DM by lowering blood glucose levels, promoting glycogen synthesis, and modulating glycolipid metabolism. Both in vitro and in vivo studies indicate that it outperformed the P. lobata extract and individual components. This study establishes the scientific validity and feasibility of utilizing the active constituent as the focus for investigating the efficacy of TCM, thereby offering novel insights and a new research paradigm for future TCM investigations. Full article

Objectives: The unknown immune-enhancing effects of steamed mature silkworms (Bombyx mori L.), known as HongJam (HJ), were investigated. Methods: Supercritical fluid extracts from the White Jade variety of HJ (WJ-SCEs) were applied to in vitro RAW264.7 macrophages (RAWMs) and ex vivo bone marrow-derived macrophages (BMDMs). Results: WJ-SCE enhanced the proliferation and viability of both RAWMs and BMDMs. Supplementation with WJ-SCE significantly reduced the lipopolysaccharide (LPS)-induced expression of iNOS mRNA and protein, resulting in decreased nitric oxide (NO) production. Additionally, WJ-SCE lowered the mRNA and protein expression of COX-2 and reduced the levels of pro-inflammatory cytokines. The mitochondrial function, ATP levels, and reactive oxygen species levels in LPS-treated macrophages were restored following WJ-SCE treatment. WJ-SCE modulated LPS-Toll-like receptor-4 (TLR-4) signaling by reducing the levels of phosphorylated (p)-p38, p-ERK1/2, and p-p65. WJ-SCE also restored gene expression related to cytokines, chemokines, glucose transport, mitochondrial metabolism, and TLR-4 signaling, suggesting the inhibition of pro-inflammatory M1 macrophage polarization. Furthermore, WJ-SCE enhanced macrophage phagocytic and pinocytotic activity. Conclusions: WJ-SCE demonstrated anti-inflammatory effects by inhibiting LPS-induced M1 polarization in both macrophage types, potentially suppressing chronic inflammation while enhancing phagocytosis and pinocytosis. Full article