Planta medica最新文献

Ovatodiolide, a macrocyclic diterpenoid isolated from the traditional Chinese medicinal herb Anisomeles indica, exhibits diverse pharmacological activities in recent research. Its antitumor effects involve modulation of key signaling pathways (e.g., NF-κB/MMP-9, JAK2/STAT3, PI3K/AKT/mTOR, and Wnt/β-catenin) and effective targeting of cancer stem cells. For anti-fibrotic activity, it suppresses the TGF-β pathway and directly inhibits glucose-6-phosphate dehydrogenase. Additionally, it demonstrates antiviral, antibacterial, and anti-inflammatory activities. This review comprehensively summarizes current knowledge on ovatodiolide, including its discovery, synthesis, pharmacological actions, and underlying molecular mechanisms against target diseases. A deeper understanding of ovatodiolide's multifaceted pharmacological activities and mechanisms of action will accelerate its clinical translation as a therapeutic agent.

Plantago major extracts have demonstrated considerable efficacy in promoting wound healing. However, there is limited research evaluating the angiogenic potential of P. major extract using Matrigel-based assays alongside gene expression analysis of key angiogenic markers such as vascular endothelial growth factor A and vascular endothelial growth factor receptor 2. This study evaluated the angiogenic effects of P. major extracts obtained by several extraction techniques: ultrasound-assisted extraction for leaves and both ultrasound-assisted extraction and maceration for non-leaf components using in vitro human umbilical vein endothelial cells. Aucubin content was analyzed using an HPTLC-densitometer, revealing the highest aucubin content in the non-leaves extract obtained from ultrasound-assisted extraction (16.75%). Furthermore, an in vitro experiment with human umbilical vein endothelial cells was conducted to assess P. major extract's effect on cell viability, migration, and the formation of capillary-like structures (tube formation). All extracts maintained cell viability above 80% at concentrations below 250 µg/mL. The leaves extract obtained from ultrasound-assisted extraction at 31.25 µg/mL showed the greatest wound closure (80.29%) and the highest branching length (2756.41 cm). However, gene expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 showed no significant upregulation in the leaves extract obtained from ultrasound-assisted extraction-treated group, and low replication numbers limited some assays. These findings suggest that P. major leaf extract may promote angiogenesis through mechanisms beyond vascular endothelial growth factor signaling, but further studies with higher statistical power and broader mechanistic approaches are warranted.

HMPs derived from Hypericum perforatum, herba (St. John's wort) play an important role in treating mild to moderate depressive episodes and mental exhaustion, for example. The genotoxic safety of these HMPs has already been assessed and reviewed in recent years. However, further data on the genotoxic potential of Hypericum perforatum, herba preparations would allow the evaluation of the therapeutic safety of the herbal drug and preparations thereof in accordance with the genotoxicity guideline of the HMPC of the EMA. Accordingly, their genotoxic potential was tested using the "bracketing and matrixing" concept, whereby extracts are tested at and between the extremes of their extraction solvents (ranging in strength from polar to non-polar) to cover the entire spectrum of the drug's constituents. In the present study, five dry extracts of Hypericum perforatum, herba, representing the full range of potential extraction solvent polarities (water, ethanol 50% (v/v), methanol 80% (v/v), ethanol 80% (v/v), and n-heptane) were tested using the Ames test, according to the OECD and HMPC guidelines. No mutagenic effects were observed for any of the five test strains in two independent experiments (plate incorporation test and pre-incubation test) each carried out with and without metabolic activation, even at the highest concentrations (5000 µg/plate), in accordance with the OECD guideline No. 471.

The study aims to investigate the pharmacodynamics and pharmacokinetics to elucidate the mechanism of enhanced anticoagulant effect of scutellarin and its preparations on warfarin. Evaluation of pharmacodynamic effects is undertaken by measuring coagulation parameters prothrombin time (PT) and activated partial thromboplastin time (APTT). The UHPLC-ESI-MS/MS method is used to determine the plasma concentrations of R/S-warfarin to investigate the influence on the pharmacokinetics. Changes in the plasma protein binding rate of warfarin is studied by ultrafiltration. The results of pharmacodynamics showed that there was no significant difference in PT, international normalized ratio (INR), and APTT between the scutellarin control and the blank control group. Compared to the warfarin control group, scutellarin co-administered with the warfarin group has a significant increase in PT and INR after 8 h, and APTT had no change. The pharmacokinetic results showed that there was an increase in peak concentration (C _max) and area under curve (AUC _0-t and AUC _0-∞) and a significant prolongation of half time (t _1/2) and a decrease in apparent clearance (CL/F) of R-warfarin compared with the warfarin control group. Compared with the warfarin group, the protein binding rates were decreased in all doses of scutellarin co-administered with the warfarin groups, respectively. Scutellarin can enhance the anticoagulant effect of warfarin by both inhibition of the R-warfarin metabolism and reduction in the protein binding rate of warfarin.

Many lignans exhibit antiproliferative effects against cancer cells, but it is rarely reported for threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-methoxypropanol (THMP), an edible red-pepper-derived lignan. This study evaluates the antiproliferative effects and mechanism of THMP against bladder cancer cells (BFTC905 and T24) regarding ATP content and flow cytometry assays in parallel with the presence and absence of N-acetylcysteine (NAC), an oxidative stress inhibitor. THMP suppressed bladder cancer cell viability in the ATP assay, which was reverted by NAC. Regarding flow cytometry, THMP triggered subG1 arrest and enhanced annexin V-affinity intensity. This apoptotic response was further supported by the finding that THMP upregulated the activation of caspases 3, 8, and 9, which is apoptotic signaling. Moreover, oxidative stress was induced by THMP regarding the upregulation of reactive oxygen species (ROS) and mitochondrial superoxide and the exhaustion of glutathione and mitochondrial membrane potential. Regarding γH2AX and 8-hydroxy-2-deoxyguanosine detection, THMP was confirmed to have DNA damage ability. These mechanisms were alleviated by NAC. Overall, THMP is the first report demonstrating the antiproliferative effect against bladder cancer cells and clarifying its oxidative stress-dependent mechanisms.

Kaempferol, a flavonol found in various edible and medicinal plants, possesses antioxidant, anti-inflammatory, and cardioprotective properties. The vasorelaxant effects of kaempferol were assessed using isolated coronary artery rings pre-contracted with potassium chloride (30 mM). Kaempferol induced a concentration-dependent relaxation in both endothelium-intact and endothelium-denuded coronary artery rings pre-contracted with potassium chloride (30 mM), indicating that its vasorelaxant effect is primarily endothelium-independent. Inhibition of nitric oxide synthase (NOS) with L-NAME (100 µM) and cyclooxygenase (COX) with indomethacin (10 µM) did not significantly alter the relaxation response, suggesting that nitric oxide (NO) and prostaglandins play a minimal role. The BK_Ca channel blocker TEA (1 mM), ATP-sensitive potassium (K_ATP) channel blocker glibenclamide (10 µM), and inward-rectifier potassium (K_IR) channel blocker BaCl₂ (30 µM) did not significantly affect kaempferol-induced relaxation. However, inhibition with the voltage-gated potassium (K_V) channel blocker 4-aminopyridine (3 mM) significantly reduced the relaxation response, indicating the involvement of K_V channels. Furthermore, molecular analysis using RT-PCR confirmed the presence of the K_V 2.1 (KCNB1) gene in sheep coronary arteries, suggesting its role in kaempferol-mediated vasorelaxation. These findings suggest that kaempferol promotes vasorelaxation through an endothelium-independent mechanism, with partial involvement of the K_V 2.1 channel. This study supports kaempferol's therapeutic potential in cardiovascular disease, recommending its dietary inclusion as a strategy to lower the risk of cardiovascular diseases.

Ginger (Zingiber officinale) has a global use as a spice, an ingredient of beverages, food supplements (syn. dietary supplements), as well as herbal medicinal products. Since the last update of ginger in ESCOP Monographs in 2009 a significant number of papers concerning its bioactive constituents and clinical uses have been published. From this large number and selecting those references (almost 500) considered most relevant to clinical aspects and therapeutic indications, the following issues are considered to be potentially important to research on other medicinal plants: [i] quality assessment; [ii] pre-clinical (in vivo) studies; [iii] quality of clinical trials; [iv] ethnicity of clinical trial participants and [v] effects of sex-gender on activity and therapeutic indications.

Cupressuflavone (CTM-01), a potential biflavonoid isolated from Cupressus torulosa exhibited antimicrobial, analgesic, cytotoxic and wound-healing properties. The present study aims to evaluate the renoprotective effects through in vitro and in vivo models as well as elucidate the underlying mechanisms of its nephroprotective action under diabetic conditions. The in vitro effects of CTM-01 on cell viability (25, 50, and 100 µM) and intracellular ROS production were evaluated in cultured normal rat proximal epithelial cells (NRK-52E) grown under high glucose conditions (30 mM) while streptozotocin (STZ) induced rats were treated with CTM-01 at 25 mg/kg for four weeks and the effects on different biochemical, histological, and molecular parameters were studied. The oral administration of CTM-01 (25 mg/kg) in diabetic rats restored the fasting blood glucose to normal control levels and markedly ameliorated renal dysfunction as evidenced by a significant decrease in serum creatinine, urea, and albumin. Additionally, CTM-01-treated rats exhibited a significant increase in the levels of renal antioxidants such as SOD, CAT, and GSH as well as decreased MDA content against diabetic control rats and restored kidney damage in CTM-01-treated diabetic rats. Moreover, CTM-01 significantly increased the level of Nrf-2 and downregulated the expression of p-NF-κB. This novel study provides strong evidence to support the potent anti-oxidative and renoprotective properties of CTM-01 in alleviating oxidative damage and inflammation through the suppression of the Nrf-2/NF-κB signalling axis for the effective management of diabetic nephropathy.

Five compounds were isolated from Ferula assa-foetida and their beta-secretase 1 inhibitory activities were evaluated. Farnesiferol B and kamolonol showed potent beta-secretase 1 inhibitory activity with IC₅₀ values of 8.11 and 1.00 µM and competitive inhibition patterns against beta-secretase 1 with K_i values of 6.51 and 0.41 µM, respectively. In silico pharmacokinetics showed that farnesiferol B was predicted to have high gastrointestinal absorption and blood-brain barrier permeability. In cell studies, farnesiferol B and kamolonol were nontoxic to normal Madin-Darby canine kidney and neuroblastoma cells, and both showed protective effects on neuroblastoma cells for Aβ₄₂-induced neurotoxicity. In molecular docking simulations, we found that the efficacy of the compounds may be related to their interaction with the flap region and hydrogen bonding with ARG368. In addition, molecular dynamics simulation of kamolonol showed the ligand maintained its stability in interaction with the loop residues. These results show that farnesiferol B and kamolonol are potent beta-secretase 1 inhibitors with neuroprotective effects, suggesting that they are potential candidates for the treatment of neurodegenerative disorders, such as Alzheimer's disease.

Various Croton species have been traditionally used to treat diabetes; however, the antidiabetic potential and safety of many of these species remain poorly understood. This study evaluated the chemical composition, antihyperglycemic activity, insulin-sensitizing effect, and acute oral toxicity of C. ehrenbergii. Dichloromethane, ethyl acetate, n-butanol, and aqueous residue fractions were obtained via liquid-liquid extraction from the hydroalcoholic extract obtained via maceration of the aerial parts. The primary compounds isolated from the fractions using column chromatography and identified by 1D nuclear magnetic resonance spectroscopy were 7,4'-di-O-methylnaringenin, β-sitosterol, tiliroside, rutin, nicotiflorin, isoquercetin, and l-quebrachitol. The in vivo antihyperglycemic activity of these compounds was assessed using oral sucrose and glucose tolerance tests, and the most active fractions were evaluated ex vivo to explore the mechanisms of action. The extract, fractions, and compounds were tested in vitro for their ability to inhibit α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) as well as for their agonistic activity on PPAR-γ. Tiliroside and nicotiflorin moderately inhibited PTP1B and α-glucosidase; whereas, l-quebrachitol acted as a PPAR-γ agonist. Acute oral toxicity studies indicated that the extract was safe at the tested dose. These results provide the first scientific evidence of the antihyperglycemic properties and preliminary safety of C. ehrenbergii.