Chronic wounds represent a persistent clinical challenge due to prolonged inflammation and impaired tissue repair mechanisms. Cannabidiol (CBD), recognized for its anti-inflammatory and pro-healing properties, shows therapeutic promise in wound care. However, its delivery via lipid nanoparticles (LNPs) remains challenging due to CBD’s inherent instability and low bioavailability. This study developed and characterized a novel hydrogel scaffold composed of CBD-loaded LNPs (CBD/LNPs) integrated into a polyvinyl alcohol (PVA) and sodium alginate (SA) matrix, designed to enhance wound repair and mitigate inflammation. The characteristics of the hydrogel scaffold were observed including the degree of swelling and LNPs’ release profiles. Furthermore, in the results, CBD/LNPs displayed enhanced stability and reduced cytotoxicity compared to unencapsulated CBD. In vitro assays demonstrated that CBD/LNPs significantly promoted fibroblast migration in gap-closure wound models and reduced intracellular reactive oxygen species, supporting their potential as a biocompatible and efficacious agent for cellular repair and oxidative stress attenuation. In vivo experiments using adult male Wistar rats with aseptic cutaneous wounds revealed that treatment with CBD/LNP-PVA/SA hydrogel scaffold significantly accelerated wound closure relative to blank hydrogel controls, demonstrating a substantial reduction in the wound area over time. Histological analysis confirms notable improvements in skin morphology in wounds treated with CBD/LNP-PVA/SA hydrogel scaffold with evidence of accelerated epithelialization, enhanced collagen deposition, and increased dermal thickness and vascularization. Additionally, skin histology showed a more organized epidermal layer and reduced inflammatory cell infiltration in CBD/LNP-PVA/SA hydrogel scaffold-treated wounds, corresponding to a 35% increase in the wound closure rate by day 28 post-treatment. These findings suggest that CBD/LNP-PVA/SA hydrogel scaffolds facilitate inflammation resolution and structural wound healing through localized, sustained CBD delivery. The dual anti-inflammatory and wound-healing effects position CBD/LNP-PVA/SA hydrogel scaffold as a promising approach for chronic wound management. Future investigations are warranted to elucidate the mechanistic pathways by which CBD modulates the skin architecture and to explore its translational applications in clinical wound care.

Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg–100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg–100 µg/ml) induced concentration-dependent relaxation (EC₅₀ = 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration–response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.

Diabetic Parkinson’s disease (DP) is a progressive neurodegenerative disease with metabolic syndrome that is increasing worldwide. Emerging research suggests that cannabidiol (CBD) is a neuropharmacological compound that acts against this disease, especially CBD in nano-formulation. The safety of cannabidiol lipid nanoparticles (CBD-LNP) was evaluated by assessing in vitro cytotoxicity in neurons and therapeutic outcomes in a DP animal model, including metabolic parameters and histopathology. CBD-LNPs were fabricated by using a microfluidization technique and showed significantly lower cytotoxicity than the natural form of CBD. The DP rats were induced by streptozotocin followed by a 4-week injection of MPTP with a high-fat diet. Rats were treated orally with a vehicle, CBD, CBD-LNP, or levodopa for 4 weeks daily. As a result, vehicle-treated rats exhibited metabolic abnormalities, decreased striatal dopamine levels, and motor and memory deficits. CBD-LNP demonstrated reduced lipid profiles, enhanced insulin secretion, and restored dopamine levels compared to CBD in the natural form. CBD-LNP also had comparable efficacy to levodopa in ameliorating motor deficits and memory impairment in behavior tests. Interestingly, CBD-LNP presented migration of damaged neuronal cells in the hippocampus more than levodopa. These findings suggest that CBD-LNP holds promise as an intervention addressing both metabolic and neurodegenerative aspects of DP, offering a potential therapeutic strategy.

Nelumbo nucifera Gaertn. (Lotus) seeds have been traditionally used to treat hypertension and are reported to have antioxidant effects. The role of lotus seeds in reproductive dysfunction associated with hypertension has not yet been investigated. Therefore, we aimed to evaluate lotus seed extract (LSE) on reproductive functions in N^ω-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertension and oxidative stress in rats. Male Sprague–Dawley rats were allocated into six groups: i) normotensive rats, ii) rats treated with l-NAME (40 mg/kg), iii-vi) rats treated with l-NAME + either 10, 100, 300 mg/kg LSE or 5 mg/kg captopril for 5 weeks. Systolic blood pressure (SBP), sperm concentrations, viability and motility and the serum testosterone were measured. The morphology, malondialdehyde (MDA) and superoxide dismutase (SOD) activities were evaluated in testis and epididymis. l-NAME-treated rats exhibited high SBP (181.9 ± 6.5 mmHg, P < 0.01) and reduced SOD activities in comparison to the normal group. These were significantly improved by the administration of 10, 100, 300 mg/kg LSE or captopril (P < 0.05). l-NAME also led to a significant increase in MDA, and reductions in sperm count, viability and motility, testosterone levels, as well as the diameter and epithelial thickness of the seminiferous tubules. Treatment with 10 mg/kg LSE or captopril significantly attenuated these effects (P < 0.05), whereas 100 and 300 mg/kg LSE showed no significant differences compared to the l-NAME group. Thus, our study demonstrates that a low dose of LSE has therapeutic potential in alleviating reproductive dysfunction associated with hypertension.

Background/Objectives: Nelumbo nucifera Gaertn. (lotus) seeds have traditionally been used to treat hypertension, though their mechanisms remain unclear. This study investigated the antihypertensive effects of lotus seed extract (LSE) and its mechanisms in rats with N^ω-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Methods: Male Sprague Dawley rats received L-NAME (40 mg/kg/day) in drinking water and were treated orally with LSE (5, 10, or 100 mg/kg/day), captopril (5 mg/kg/day), or a combination of LSE and captopril (2.5 mg/kg/day each) for 5 weeks. Hemodynamic parameters and histological changes in the left ventricle and aorta were assessed. Mechanistic studies included measurements of plasma nitric oxide (NO) metabolites, malondialdehyde (MDA), superoxide dismutase (SOD) activity, angiotensin II (Ang II), angiotensin-converting enzyme (ACE) activity, and protein expression via western blot. Results: L-NAME elevated systolic blood pressure and induced cardiovascular remodeling, oxidative stress, and renin-angiotensin system activation. LSE treatment reduced blood pressure, improved antioxidant status, increased NO bioavailability, and downregulated gp91^phox and AT₁R expression. The combination of low-dose LSE and captopril produced stronger effects than LSE alone, with efficacy comparable to captopril. Conclusions: These findings suggest that LSE exerts antihypertensive effects via antioxidant activity and inhibition of the renin-angiotensin system, supporting its potential as an adjunct therapy for hypertension.

Yahom Navakot (YN), is a Thai traditional medicine, consisting of 54 plants, for treating fainting and dizziness. Thus, YN might relieve orthostatic hypotension (OH) symptoms, but its therapeutic action is unclear. Therefore, this study evaluated YN in OH rats, using a head-up tilt test (HUT). Rats were anesthetized, and OH induced via a 90^oHUT, before and after administering vehicle, a YN powder suspension (10, 100 mg/kg), a YN aqueous extract (100 mg/kg), and midodrine (5 mg/kg). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), pulse pressure (PP) and heart rate (HR) were determined via the carotid artery. Plasma noradrenaline (NA) was evaluated. YN-induced vasoconstriction of isolated rat aorta rings was determined using organ bath technique. Baseline BP increased with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine, while HR decreased, compared with vehicle and control. 90^oHUT rapidly reduced SBP, DPB and MAP, but increased HR, for control and vehicle-treated groups, but BP was steady with the 100 mg/kg YN powder suspension, the YN aqueous extract or midodrine. The 90^oHUT-increase in HR was most pronounced with the 100 mg/kg YN powder suspension (the traditional formulation). This accords with increased plasma NA. YN also induced vasoconstriction in rat aorta via α₁-receptor activation. Thus, the anti-hypotensive action of YN involved a stimulating effect on the heart and blood vessels via sympathetic activation. The results support the traditional use of YN and demonstrated the effectiveness of YN for OH prevention.