Atherosclerosis is a chronic inflammatory disorder that involves endothelial dysfunction and accumulation of inflammatory cells in the vessel intima. Approximately 32% of global mortality is attributed to cardiovascular diseases, with atherosclerosis playing a major role. Endothelial dysfunction is a key hallmark of atherosclerosis, with key mediator tumor necrosis factor‐α (TNF‐α) driving endothelial–monocyte interactions that further lead to adverse cardiovascular events. Hydroxychavicol, a phenolic compound enriched in Piper betle (PB), methanolic and chloroform extracts, has demonstrated anti‐inflammatory activity, yet its effects on endothelial activation remain insufficiently characterized. Therefore, this study aimed to investigate the endothelial‐protective effects of hydroxychavicol‐rich PB methanol (PB‐M) and chloroform (PB‐C) extracts by evaluating their impact on the expression of adhesion molecules and proinflammatory cytokines in TNF‐α‐induced human umbilical vein endothelial cells (HUVECs). HPLC was performed to confirm the presence and determine the amount of hydroxychavicol in both PB‐M and PB‐C. The cytotoxicity effects of both extracts were first assessed by MTT assay. HUVECs were pretreated with NF‐κB inhibitor BAY11‐7082, PB‐M, or PB‐C before being exposed to TNF‐α for 4 h. Adhesion molecules and cytokines expression were measured by Western blot and ELISA, respectively. Both PB‐M and PB‐C were shown to contain hydroxychavicol, yet PB‐C has about 3.8 times higher levels. MTT assays yielded IC 50 values of 128.9 µg/mL for PB‐M and 18.59 µg/mL for PB‐C, while HUVEC morphology remained normal at 100 µg/mL PB‐M and 20 µg/mL PB‐C. Both extracts displayed dose‐dependent suppressing effects on TNF‐α‐induced E‐selectin, VCAM‐1, and ICAM‐1 expression. PB‐M resulted in a pronounced inhibition of IL‐6, IL‐8, and MCP‐1, while PB‐C displayed cytokine‐selective suppressive effects. In conclusion, both PB‐M and PB‐C attenuated TNF‐α‐induced endothelial inflammation, with PB‐C acting at lower effective doses but PB‐M providing broader anti‐inflammatory suppression, suggesting that their different phytochemical compositions and possible synergistic interactions beyond hydroxychavicol may contribute to their distinct bioactivities, warranting further investigations.
Lung cancer is one of the most common malignancies worldwide, and due to its high mortality rate and resistance to treatment, there is an urgent need to develop effective treatments with low toxicity. Long stephania herb (LSH) is a tropical herb used clinically for the treatment of inflammation and analgesia, but its antitumor effects are unknown. In this study, UHPLC–OE–MS was used to detect the chemical components of LSH; the cytotoxic effects of these chemical components on normal lung cells and non-small cell lung cancer (NSCLC) cell lines were observed in vitro cell experiments, and the inhibitory effects of LSH on the growth of NSCLC were detected in animal tumor models. The possible molecular targets of LSH for NSCLC were predicted by network pharmacology and molecular docking. The results showed that LSH has more than a thousand chemical components; at the microgram level per milliliter, it can effectively inhibit the proliferation, migration, and invasion of lung cancer A549 cells and promote apoptosis in these cells. It also can effectively inhibit the growth of tumors in vivo and has no significant toxic effects on normal lungs, liver, heart, and kidneys. Analysis showed that 20 pharmacodynamic components of LSH may target EGFR, PIK3CA, PIK3R1, AKT1, HSP90AA1, SRC, MAPK1, MAPK3, STAT3, JUN, and CASP3. Inhibition of the PI3K/AKT signaling pathway and proteoglycans in cancer and other signaling pathways plays an anti-NSCLC role. In conclusion, this study is the first to report the efficacy of LSH in the treatment of NSCLC, and it is a very valuable tropical medicinal plant for the treatment of lung cancer.
Ethnopharmacological Relevance The Thai traditional medicine “Ya‐Tard Aob‐Choei” (AC) is a polyherbal remedy used for the treatment of gastrointestinal disorders. Its traditional liquid dosage form has practical limitations, including inconsistent appearance and difficulties in handling and transportation. This study aimed to develop a chewable dosage form of AC with satisfactory physicochemical properties and to evaluate the retention of selected marker compounds, including gallic acid (GA), cinnamaldehyde (CMD), eugenol (EUG), and glycyrrhizic acid (GZ). Materials and Methods Formulation studies were conducted to identify suitable excipients for the preparation of AC powder and chewable tablets, and the resulting formulations were evaluated for their physicochemical properties. A validated high‐performance liquid chromatography (HPLC) method was used to determine the selected marker compounds and compare the phytochemical profile of the developed formulation with liquid AC preparations, including a self‐prepared reference formulation and commercially available products. Results The formulation containing maltodextrin DE 18 at an extract‐to‐carrier ratio of 1:2 exhibited optimal powder characteristics for tablet production, and isomalt was identified as an effective diluent–binder for the preparation of chewable tablets with satisfactory physicochemical properties. HPLC analysis revealed compound‐specific changes during conversion from the liquid‐to‐solid dosage form. GA was relatively well preserved (5.25 mg/dose), whereas EUG, CMD, and GZ decreased by approximately 99%, 35%, and 33%, respectively, compared with the self‐prepared liquid formulation (P7). Conclusion A chewable AC tablet with satisfactory physicochemical properties was developed; however, conversion to the solid dosage form resulted in compound‐specific losses, particularly of EUG. Further process optimization is required to improve the retention of volatile and heat‐sensitive constituents. This formulation approach may nevertheless offer a pragmatic strategy for the development and standardization of other traditional Thai herbal medicines, although dedicated stability and sensory studies are needed to establish product stability and acceptability.
Siltartoxatug—developed by Trinomab Pharmaceutical Co., Ltd., using its proprietary HitmAb® platform—is the first-in-class recombinant monoclonal antibody drug for urgent prophylaxis of tetanus approved by China National Medical Products Administration in February 2025, which addresses the critical unmet need to substitute blood-derived passive immunization preparations for prevention of tetanus. The nonclinical pharmacokinetic and immunogenicity study of siltartoxatug was designed and conducted in strict compliance with global regulatory guidelines for initiating the first-in-human clinical trials. Herein, we report the comprehensive findings from this study. Twenty-four naive cynomolgus monkeys (Macaca fascicularis) were randomly assigned to four groups each with 6 animals. Monkeys in Group 1 received intravenous infusion of siltartoxatug at 1 mg/kg. Monkeys in Groups 2, 3, and 4 received intramuscular injection of siltartoxatug at dose of either 1 mg/kg, 3 mg/kg, or 10 mg/kg. Blood samples were collected over 57 days post-administration, and serum drug concentrations and anti-drug antibody levels were determined with validated methods. Results showed that intramuscular administration of siltartoxatug exhibited favorable pharmacokinetic characteristics: primarily systemic distribution with high bioavailability (88.0% at 1 mg/kg) and low apparent volume of distribution (58.7–69.4 mL/kg), prolonged elimination half-life (11.7–12.4 days), short mean time to maximum concentration (1.2–2.7 days), and dose-dependent systemic exposure without significant sex differences. Additionally, minimal anti-drug antibody responses were observed. These findings underpinned greater predictability for its clinical translation and informed its first-in-human development.
Plant extracts and microbial-derived molecules, particularly oligo- and polysaccharides, are known to promote tissue repair. Triticum vulgare extract (TVE), derived from germinated whole plants and utilized in medical devices, is rich in bioactive molecules comprised of oligo- and polysaccharides with diverse biological properties beneficial for wound repair. This study investigates the biochemical mechanisms underlying TVE’s proregenerative activity in vitro effects, comparing it with hyaluronic acid (HA), a gold standard in wound healing. Preliminary results showed that TVE has scavenging properties/antioxidant activity also at lower concentrations with respect to HA that has long been recognized for these properties (Galvez-Martin et al.). In vitro assays evaluated cell proliferation, migration, extracellular matrix biomarkers, and responses to stress in 2D and 3D models. TVE significantly enhanced keratinocyte migration, reaching approximately 50% wound closure in less than 20 h, whereas the untreated control required about 30 h to achieve the same level of closure. Moreover, TVE performed better than HA at low concentrations, while both treatments improved HDF proliferation and ECM biomarker expression. More specifically, COL1 expression was upregulated by 2.3-fold relative to the control, showing an effect comparable to that induced by HA (2.8-fold). Conversely, ELS expression exhibited a 2.0-fold increase in response to TVE and a 2.6-fold increase following HA treatment compared with the control. In addition, the extract significantly increased HBD-2 expression by 2-fold relative to the control, a novel finding that may be relevant, given the role of this antimicrobial peptide in innate immunity, inflammation regulation, and wound repair. Under stressful conditions, including dehydration and exposure to reactive oxygen species, TVE showed protective effects comparable to HA in both HDF and HaCaT cells. 3D skin models, including those treated with LPS, confirmed the results of 2D assays, further validating TVE’s biological properties. Overall, these studies demonstrate that this extract exerts biological effects comparable to pharmaceutical HA in several in vitro skin models. These findings further support the potential application of TVE in wound management and skin regenerative approaches.
