Hepatitis is an inflammatory condition that can develop hepatocellular carcinoma. Traditional medicine has always been the pillar of medical practice. However, it became less compatible with the current understanding of the diseases and the possible treatment. Therefore, in silico tools could be utilized for building the bridge between the legacy of the past and the current medical approaches allowing access to new therapeutic discoveries. In this work, a Chinese traditional medicine database was screened using structure-based virtual screening to identify molecules that could inhibit p38 alpha mitogen-activated protein kinase (MAPK). Out of the identified compounds, four selected compounds: chrysophanol, physcion, curcumin and hesperidin were isolated from their respective sources and their structures were confirmed by spectroscopic methods. These compounds decreased the gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1β) in lipopolysaccharide (LPS) induced inflammation in a hepatocellular carcinoma cell line (HepG2) in a dose-dependent manner. The molecular docking study revealed the specificity of these compounds towards p38 MAPK rather than other MAPKs. In conclusion, the molecular and in silico studies suggest that the isolated compounds could be a potential treatment for hepatitis by resolving inflammation controlled by MAPKs, thus limiting the development of further complications and lower side effects.

Background: In Jordanian traditional medicine, Clematis cirrhosa is commonly employed for the management of different diseases. Numerous investigations have documented the cytotoxic properties of different Clematis species against numerous types of cancer. Previously, we demonstrated the potential cytotoxicity of Clematis cirrhosa against HT-29 colorectal cancer cells. Extending our work, the current research aimed to explore the possible mechanisms underlying its antiproliferative activity with a plant safety evaluation. Methods: This study evaluates the extract’s impact on the cell cycle, apoptosis, and cell migration through in vitro assays, LC-ESI-QTOF-MS/MS analysis, docking studies, and an acute toxicity evaluation. Results: The Clematis cirrhosa ethanol extract (CEE) induced G2/M phase cell cycle arrest (19.63%), triggered significant apoptosis (41.99%), and inhibited cell migration/wound healing by 28.15%. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed increased expression of the proapoptotic markers BAX (6.03-fold) and caspase-3 (6.59-fold), along with the reduced expression of the antiapoptotic BCL-2, in CEE-treated cells. Moreover, CEE significantly restrained angiogenesis by reducing VEGF mRNA expression by 63.9%. High-resolution LC-ESI-QTOF-MS/MS studies identified 26 metabolites, including phenolic compounds, fatty acids, and triterpenoids. Docking studies suggested that manghaslin had the highest binding affinity for VEGFR-2, followed by calceolarioside B, quercetin 7-O-rhamnopyranoside, luteolin, and quercetin-3,7-O-diglucoside. On the other hand, salvadoraside exhibited the highest binding affinity for the inhibition of caspase-3, followed by quercetin-3,7-O-diglucoside, kaempferol-3,7-O-α-L-dirhamnoside, manghaslin, and tectoridin, supporting the observed apoptotic effects. Interestingly, the outcomes further indicate that a single oral administration of up to 5000 mg/kg CEE is safe for consumption. Conclusions: These outcomes point to the potential of Clematis cirrhosa as a promising candidate for further exploration in cancer therapy.

The incorporation of cisplatin (CP) as a cytotoxic antineoplastic agent in most chemotherapeutic protocols is a challenge due to its toxic effect on testicular tissues. Natural compounds present a promising trend in research, so a new nutraceutical formulation (NCF) was designed to diminish CP spermatotoxicity. A combination of three nutraceutical materials, 250 mg Spirulina platensis powder (SP), 25 mg Tribulus terrestris L. extract (TT), and 100 mg fish oil (FO) were formulated in self-nanoemulsifying self-nanosuspension (SNESNS). SP was loaded into the optimized self-nanoemulsifying system (30% FO, 50% span 80/cremophor EL and 20% isopropanol) and mixed with TT aqueous solution to form SNESNS. For the SP, phytochemical profiling revealed the presence of valuable amounts of fatty acids (FAs), amino acids, flavonoids, polyphenols, vitamins, and minerals. Transmission electron microscopy (TEM) and particle size analysis confirmed the formation of nanoemulsion-based nanosuspension upon dilution. Method validation of the phytochemical constituents in NCF has been developed. Furthermore, NCF was biologically evaluated on male Wistar rats and revealed the improvement of spermatozoa, histopathological features, and biochemical markers over the CP and each ingredient group. Our findings suggest the potential of NCF with SNESNS as a delivery system against CP-induced testicular toxicity in male rats.

Background: The present study aims to enhance the wound healing potential of the seed oil (SO) of Lagenaria siceraria (Egyptian cultivar) via the preparation of SO-loaded binary nanoethosomal (SO-BNE) gels. SO-BNEs were prepared using 2³ factorial design, characterized for vesicle size, zeta potential, polydispersity index, linoleic and oleic acid EE% for ensuring improved skin permeability. The L. siceraria SO, optimized SO-BNE gels (0.5% and 5%) and Mebo® were topically applied in full-thickness wounded rat model twice daily for 10 days. Results: In the SO-BNE gel groups, the normal appearance of the skin architecture and structure of the dermis was revealed. In addition, the levels of NRF2, TGF-β1 and FOXO1, collagen type I, SMA-α and MIP2 were significantly elevated. The wound healing potential of SO-BNE gels was proposed to be via suppression of oxidative stress and stimulation of skin regeneration biomarkers. Furthermore, the SO screening through GC/MS unveiled high percentages of unsaturated fatty acids. SO was also found to be nontoxic to human skin fibroblast cells; enhanced viability and migration rates at concentration of 50 g/mL by 99.76% and 75.9%, respectively. Conclusion: These findings demonstrate that the Lagenaria siceraria SO-loaded BNE gels represent a promising delivery for wound healing with enhanced release and bioavailability.