Pharmaceutical Biology最新文献

Context: The use of herbal products in Malawi remains widespread and culturally significant, often occurring alongside pharmaceutical medicine treatments. As the burden of non-communicable diseases such as diabetes and hypertension continues to rise, the potential for herbal-drug interactions (HDIs) represents an underexamined public health concern.

Objective: Evaluate the concurrent use of herbal products and pharmaceutical medicines among patients with diabetes or hypertension in a large health care facility in Malawi and identify potential adverse HDIs.

Materials & methods: An exploratory mixed-methods, cross-sectional study was conducted with 301 patients attending a diabetes or hypertension clinic at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants self-reported herbal and pharmaceutical use, and a targeted literature review was undertaken to assess potential pharmacokinetic and pharmacodynamic interactions between commonly reported herbal products and prescribed medications.

Results: Participants reported concurrent use of a wide variety of herbal products (e.g., garlic, ginger, okra, lemon, mango, moringa) with prescription medicines (e.g., metformin, insulin, glibenclamide, hydrochlorothiazide, enalapril, amlodipine). While clinical outcomes were not independently verified, literature review findings, in some cases, indicated meaningful potential for HDIs.

Discussion and conclusion: This study provides foundational data on herbal-pharmaceutical co-use in Malawi and highlights the need for expanded research, improved documentation of herbal use in healthcare settings, and improved education for patients and providers. Integrating awareness of herbal product use into clinical care is essential, and the methodology and findings may inform future hypothesis-driven studies across Africa and other regions where traditional and modern medicine use overlaps.

Context: Apigenin, a naturally flavonoid, is reported to have protective effects in chronic and metabolic diseases. But the therapeutic or ameliorative effects of apigenin on atherosclerosis are not known.

Objective: Our study aimed to elucidate the underlying mechanism of apigenin on preventing atherosclerosis by enhancing selective autophagy/lipophagy and promoting RCT process.

Materials and methods: ApoE^-/- mice fed with a high-fat diet (HFD) for 18 weeks were used to establish atherosclerosis model. Oil-Red-O staining of the plaques in the aorta and the heart was used to determine the severity of atherosclerosis. The autophagy flux was evaluated by western blot and reverse transcription quantitative PCR (RT-qPCR). Then triton WR-1339 (TWR) was injected into muscles of C57BL/6 mice, and the role of autophagy was assessed by autophagy inhibitor LY294002 intervention. The transmission electron microscopy (TEM) and immunofluorescence microscopy analysis (IFM) were used to elucidate the lipid-lowering mechanism of apigenin.

Results: In HFD-induced mice, apigenin inhibited the dangerous progression of atherosclerosis through decreasing lipid deposition in plaques, lowering serum and liver lipid contents, activating autophagy and promoting reverse cholesterol transport (RCT). In TWR-induced mice, apigenin reduced the serum and liver lipid levels, enhanced the autophagy flux and increased RCT, but the above effects of apigenin were weakened by LY294002. The TEM and IFM images revealed that apigenin promoted the formation of autophagosomes and the co-localization between autophagy proteins with lipid protein.

Discussion and conclusions: The lipid-lowering effects of apigenin were mediated through promoting RCT and enhancing selective lipophagy, meanwhile it provided a potential therapeutic option for atherosclerosis.

Context: Antibiotic resistance in bacteria is a growing global problem, with biofilm formation and efflux pumps playing crucial roles in this issue.

Objective: This study explores the effects of phenolic compounds of Origanum majorana against Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) strains by inhibiting biofilm formation and efflux pumps.

Materials and methods: The methanolic extract of O. majorana was fractionated guided by an antibiofilm assay, and the active fractions were analyzed by multistep chromatographic separation to yield five pure compounds. Their structures were then determined using 1D and 2D nuclear magnetic resonance spectroscopy. The minimum inhibitory concentrations of the extracts, fractions, and isolated compounds were determined via the microdilution method in a 96-well plate. Antibiofilm activity was assessed using the crystal violet method, and the effect on efflux pumps was tested by a real-time ethidium bromide accumulation assay.

Results: Arbutin (1), apigenin 7-O-glucoside (2), 6'-caffeoylarbutin (3), rosmarinic acid (4), and 2-deoxy-d-1,4-ribonolactone (5) were isolated from the aqueous methanolic extract. Compounds 1, 2, and 4 reduced E. coli biofilm formation by 24.82%-42.98% at 100 µM, whereas only arbutin (1) moderately suppressed biofilm formation of MRSA (23.15 ± 1.56% at 50 µM). Arbutin also demonstrated efflux pump inhibitory activity against MRSA (relative fluorescence index of 0.49 at 100 µM).

Discussion and conclusions: The newly discovered natural antibiofilm agents show promise as candidates for treating biofilm-associated infections and combating antibiotic-resistant bacteria.

Context: Tanshinone IIA (Tan IIA), a bioactive compound derived from the traditional Chinese herb Salvia miltiorrhiza (Family Lamiaceae, Authority Bunge), is well-known for its protective effects in various kidney diseases. However, its role in obstructive nephropathy has not been thoroughly investigated.

Objective: This study aimed to explore the protective effects of Tan IIA in a mouse model of unilateral ureteral obstruction (UUO) and to elucidate the cellular and molecular mechanisms underlying these effects.

Materials and methods: Gasdermin D (GSDMD) knockout mice and their wild-type (WT) littermates underwent UUO surgery, with Tan IIA treatment administered 24 h prior. Human proximal tubular cells (HK-2 cells) were treated with TGF-β1 to induce fibrosis (50 ng/mL for 24 h), followed by Tan IIA treatment (5 μM) for an additional 3 h.

Results: Tan IIA significantly reduced the expression of extracellular matrix (ECM) components, including collagen I, α-smooth muscle actin (α-SMA), vimentin and fibronectin, in UUO mice. Tan IIA attenuated GSDMD-mediated pyroptosis. However, in GSDMD knockout mice subjected to UUO, the protective effects of Tan IIA on ECM gene expression and collagen deposition in the tubular interstitium were reduced. In vitro studies showed that Tan IIA reduced GSDMD activation and fibronectin protein expression in HK-2 cells.

Discussion and conclusions: Tan IIA may mitigate GSDMD-mediated pyroptosis in renal tubular epithelial cells (RTECs) and reduce kidney fibrosis, highlighting its potential as a therapeutic strategy to prevent the progression of kidney disease after ureteral obstruction.

Context: Kratom (Mitragyna speciosa), native to Southeast Asia, has traditionally been consumed as fresh leaves or teas. Under those conditions, exposure to 7-hydroxymitragynine (7-OH)-a potent μ-opioid receptor agonist-is minimal, as it occurs only at trace levels in leaf material. By contrast, the U.S. market offers chemically enriched or semi-synthetic 7-OH products, often marketed as 'kratom' yet chemically distinct from botanical preparations.

Methods: '7-OH', '7-hydroxymitragynine', and 'kratom' were used as keywords; relevant literature was obtained from PubMed, Web of Science, and Google Scholar.

Results: Pharmacological studies consistently identify 7-OH as a partial μ-opioid receptor agonist with nanomolar affinity, greater efficacy than mitragynine, and often exceeding the potency of morphine. Animal experiments demonstrate robust antinociceptive effects, respiratory depression, tolerance, dependence, and reinforcing properties characteristic of opioids. Human pharmacokinetic studies show systemic exposure after kratom ingestion, but concentrated 7-OH products bypass metabolic formation, producing markedly higher exposures. Regulatory surveillance, poison-center data, and marketplace audits confirm a rapid increase in availability and use of these products. State health departments have reported severe intoxications and fatalities. Clinical cases describe escalating use, medically managed withdrawal, and psychiatric destabilization, while forensic investigations document postmortem concentrations consistent with fatal opioid toxicity. Pediatric risk is amplified by developmental susceptibility, absence of age restrictions, and marketing in confectionary formats. Emerging analogues such as MGM-15 further extend this trajectory.

Conclusion: Collectively, the evidence demonstrates that concentrated 7-OH products are pharmacologically and toxicologically distinct from kratom leaf and pose significant risks of morbidity and mortality under typical conditions of use.

Context: Macrophages play a critical role in the pathogenesis of ulcerative colitis (UC). Indirubin (IDR), a natural ligand of the aryl hydrocarbon receptor (AhR), has been shown to ameliorate DSS-induced colitis in our previous study (Liu Z et al.).

Objective: To investigate whether IDR exerts its protective effects by regulating M1/M2 polarization and inhibiting ferroptosis in macrophages.

Materials and methods: Immunohistochemistry staining targeting CD206 and F4/80 was performed to evaluate the effect of IDR on the polarization of M1/M2 macrophages in colitis. Subsequently, the effects of IDR on the M1- or M2-polarization of THP-1-derived macrophages were investigated. Furthermore, the effects of IDR on ferroptosis in the colon tissue of mice and on RSL3-induced ferroptosis in THP-1-derived macrophages were assessed. The results were verified in mouse peritoneal macrophages.

Results: In addition to reducing the infiltrated macrophages, IDR treatment preserved CD206+ macrophages in DSS-induced colitis. Using cultured THP-1 cells, we demonstrated that IDR inhibited M1 polarization and prompted M2 polarization. Furthermore, we showed that IDR treatment decreased levels of 4-HNE while increasing GPX4 and NRF2 in DSS-induced colitis and THP-1 cells. IDR treatments also reduced cellular reactive oxygen species (ROS) and iron content, and mitigated RSL3-induced ferroptosis in THP-1-derived macrophages. Similarly, IDR augmented M2-polarization and alleviated ferroptosis in peritoneal macrophages.

Discussion and conclusion: IDR skews the polarization of macrophages from M1 to M2. Furthermore, it inhibits ferroptosis in both mice and THP-1-derived macrophages. These mechanisms may contribute to the therapeutic effects of IDR in the treatment of UC.

Context: The Atlas Pistachio (Pistacia atlantica Desf.) possesses numerous applications for therapeutic purposes.

Objective: We set out to test various extracts from Pistacia atlantica Desf. fruits and leaves for their anticancer and acetylcholinesterase inhibitory effects. In addition to discovering the phytochemical profile of P. atlantica extracts responsible for the pharmacological effects that were researched.

Materials and methods: The anti-acetylcholinesterase activity was performed against the acetylcholinesterase (AChE) enzyme. Anticancer assays were investigated by evaluating the antiproliferative and cytotoxicity potentials against five cancerous cell lines using the [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MMT:Medical training therapy) assay. The phenolic profile was established against phenolic standards using high-performance liquid chromatography with diode-array detection (HPLC-DAD).

Results: In anticholinesterase activity, the extracts of P. atlantica inhibited AChE activity in a dose-dependent manner. The stronger AChE inhibition activity was obtained for the n-BuOH extract of the fruits (IC₅₀ 47.80 ± 1.03 µg/mL) and compared to the leaf extracts. The results, compared with galantamine, showed a close inhibition activity. P. atlantica extracts also showed the most optimal antiproliferative and cytotoxic effect against cancer cell lines compared to positive control 5FU (Fluorouracil); the best antiproliferative activity was obtained for the fruit extracts compared to the leaf extracts. The spotted biological activities can be attributed to flavonoids and phenolic compounds in the extracts. The HPLC-DAD analysis identified the presence of 18 phytochemicals. The main compounds detected were luteolin, gallic acid, epicatechin, and protocatechuic acid.

Discussion and conclusion: This study demonstrated moderate anticholinesterase and suitable antiproliferative activities of P. atlantica Desf. extracts, which opens up new possibilities for the pharmaceutical and food industries.This study suggests that the concentrations of phenolic compounds, along with the results of anticholinesterase and antiproliferative activities found in the fruit and leaf extracts of P. atlantica Desf, indicate this plant holds promise for pharmaceutical and food application industries.

Context: Tagetes erecta is widely cultivated for its ornamental flowers and has traditionally been used as a diuretic and antihypertensive. However, its effects on blood pressure have not yet been studied.

Objective: To evaluate the vasorelaxant potential of ethanolic extract of T. erecta from two cultivars of edible flowers, yellow and orange.

Materials and methods: The pharmacological effects of T. erecta extracts as vasorelaxant agents were evaluated using isolated rat aorta rings in an organ bath and by measuring the pharyngeal pumping rate in the Caenorhabditis elegans model.

Results: The extracts induced relaxation in endothelium-intact aortic rings pre-contracted with different agents. Vasorelaxant effect was attenuated by endothelial removal and by pretreatment with L-NAME or ODQ, but not by indomethacin. Statistically significant effects were observed only at low concentrations. Atropine and H-89 reduced the extract-induced response, whereas okadaic acid had no effect. In a calcium-free medium, the extracts reduced contractions induced by CaCl₂ and phenylephrine. Relaxation was significantly attenuated by iberiotoxin, glibenclamide, BaCl₂, and 4-aminopyridine, while apamin and TRAM-34 had mild effect. The extracts also significantly decreased the pharyngeal pumping rate in C. elegans.

Discussion and conclusion: The extracts induced concentration-dependent vasorelaxation though both endothelium-dependent and -independent mechanisms. At low concentrations, relaxation was mediated by nitric oxide, while at higher concentrations it involved inhibition of intracellular Ca²⁺, opening of K⁺ channels, and activation of protein kinase A. In C. elegans, the extracts significantly reduced pharyngeal pumping. This study is the first to suggest that T. erecta could be beneficial in treating pathologies associated with endothelial dysfunction, such as hypertension.