Nimbolide: promising agent for prevention and treatment of chronic diseases (recent update).

Background: Nimbolide, a bioactive compound derived from the neem tree, has garnered attention as a potential breakthrough in the prevention and treatment of chronic diseases. Recent updates in research highlight its multifaceted pharmacological properties, demonstrating anti-inflammatory, antioxidant, and anticancer effects. With a rich history in traditional medicine, nimbolide efficacy in addressing the molecular complexities of conditions such as cardiovascular diseases, diabetes, and cancer positions it as a promising candidate for further exploration. As studies progress, the recent update underscores the growing optimism surrounding nimbolide as a valuable tool in the ongoing pursuit of innovative therapeutic strategies for chronic diseases. Methods: The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus and Web of Knowledge databases. Results: Most studies have shown the Nimbolide is one of the most potent limonoids derived from the flowers and leaves of neem (Azadirachta indica), which is widely used to treat a variety of human diseases. In chronic diseases, nimbolide reported to modulate the key signaling pathways, such as Mitogen-activated protein kinases (MAPKs), Wingless-related integration site-ß (Wnt-ß)/catenin, NF-κB, PI3K/AKT, and signaling molecules, such as transforming growth factor (TGF-ß), Matrix metalloproteinases (MMPs), Vascular Endothelial Growth Factor (VEGF), inflammatory cytokines, and epithelial-mesenchymal transition (EMT) proteins. Nimbolide has anti-inflammatory, anti-microbial, and anti-cancer properties, which make it an intriguing compound for research. Nimbolide demonstrated therapeutic potential for osteoarthritis, rheumatoid arthritis, cardiovascular, inflammation and cancer. Conclusion: The current review mainly focused on understanding the molecular mechanisms underlying the therapecutic effects of nimbolide in chronic diseases.

Potential Treatment of Dermatophyte Trichophyton rubrum in Rat Model Using Topical Green Biosynthesized Silver Nanoparticles with Achillea santolina Extract.

Trichophyton rubrum is the most common dermatophyte, and can cause cutaneous infections in humans and animals (dermatophytosis). In this study, we investigated the anti-dermatophytic potential of green synthesized silver nanoparticles using Achillea santolina extract (AS-AgNPs) in an in vitro and in vivo rat model of dermal T. rubrum dermatophytosis (TRD). The green synthesis of AS-AgNPs was performed using A. santolina extract and characterized by UV-VIS spectroscopy, zeta potential, imaging (transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Energy dispersive X-ray analysis (EDX). The antifungal activity of AS-AgNPs was determined by the broth microdilution method, conidial germination, and hyphal growth inhibition. TEM and SEM were used to study the mode of the antifungal action of AS-AgNPs. AS-AgNPs inhibited the growth of T. rubrum with an MIC of 128 µg/mL, and suppressed the conidial germination and hyphal growth by 55.3% 84.6%, respectively. AS-AgNPs caused modified mycelial structures, increased cell membrane permeability, and cell wall damage. AS-AgNPs significantly increase the permeability of the fungal membrane, as revealed by reducing ergosterol biosynthesis. An increase in the intracellular ROS and the induction of apoptosis were also observed during AS-AgNP treatment. In addition, AS-AgNPs reduced the cell wall integrity, as shown by the reduction in the ß-(1,3)-d-glucan synthase and chitin synthase activities. AS-AgNPs showed very low toxicity on primary human dermal fibroblasts (HDF) at the MIC. The topical treatment of the infected skin in the TRD rat model with AS-AgNPs showed a significant reduction in the fugal burden after 7 days and a complete clearance of fungal conidia, with a high recovery of epidermal and dermal structures after 14 days, compared to control rats. Interestingly, AS-AgNPs significantly attenuated the infiltrated inflammatory cells, in association with reducing the tissue proinflammatory cytokines including TNF-α, IL-1, IL-6, MOP and IL-17. In conclusion, our data prove AS-AgNPs to be a novel green topical therapy for dermatophytosis caused by T. rubrum.

Therapeutic Effect of Green Synthesized Silver Nanoparticles Using Erodium glaucophyllum Extract against Oral Candidiasis: In Vitro and In Vivo Study.

Oral candidiasis (OC) is a fungal infection caused by an opportunistic fungi Candida albicans, which is found in the normal flora of healthy people. In this study, we examined the anti-candidal effect of green synthesized silver nanoparticles using leaf extract of Erodium glaucophyllum (EG-AgNPs) against C. albicans in vitro and in vivo. EG-AgNPs were synthesized for the first time using E. glaucophyllum extract and characterized by imaging (transmission electron microscopy (TEM), UV-VIS spectroscopy, zeta potential, X-ray diffraction (XRD), Energy dispersive x-ray analysis (EDX), and Fourier transform infrared spectroscopy (FTIR). A mouse model of OC was used for in vivo study. The agar well diffusion method showed the anti-candidal activity of EG-AgNPs against C. albicans with MIC 50 µg/mL. EG-AgNPs inhibited the dimorphic transition of C. albicans and suppressed the formation of biofilm by 56.36% and 52%, respectively. Additionally, EG-AgNPs significantly inhibited the production of phospholipases and proteinases by 30% and 45%, respectively. EG-AgNPs cause cytoplasm disintegration and deterioration of cell wall as imaged by SEM and TEM. Interestingly, EG-AgNPs did not display any cytotoxicity on the human gingival fibroblast-1 HGF-1 cell line at MIC concentrations. Topical treatment of the tongue of the OC mouse model with EG-AgNPs showed significant reduction in candidal tissue invasion, less inflammatory changes, and no tissue modification, in association with marked low scare and hyphal counts as compared to control group. In conclusion, our data demonstrated the potent inhibitory action of EG-AgNPs on the growth and morphogenesis of C. albicans in vitro and in vivo. Thus, EG-AgNPs represent a novel plausible therapeutic approach for treatment of OC.

Does the treatment of dried herbs with ozone as a fungal decontaminating agent affect the active constituents?

Herbs and spices are food crops susceptible to contamination by toxigenic fungi. Ozone, as a decontamination approach in the industry, has attractive benefits over traditional food preservation practices. A contribution to the studying of ozone as an antifungal and anti-mycotoxigenic agent in herbs and spices storage processes is achieved in this research. Nine powdered sun-dried herbs and spices were analyzed for their fungal contamination. The results indicate that licorice root and peppermint leaves were found to have the highest population of fungi while black cumin and fennel record the lowest population. The most dominant fungal genera are Aspergillus, Penicillium, Fusarium, and Rhizopus. Ozone treatment was performed at a concentration of 3 ppm applied for exposure times of 0, 30, 90, 150, 210, and 280 min. After 280 min of exposure to ozone, the reduction of fungal count ranged from 96.39 to 98.26%. The maximum reduction in spore production was achieved in the case of A. humicola and Trichderma viride exposed for 210 min ozone gas. There was a remarkable reduction in the production of the total mycotoxin, reaching 24.15% in aflatoxins for the 150 min-treated inoculum in the case of A. flavus. The total volume of essential oil of chamomile and peppermint was reduced by 57.14 and 26.67%, respectively, when exposed to 3 ppm. For 280 min. In conclusion, fumigation with ozone gas can be used as a suitable method for achieving sanitation and decreasing microbial load in herbs and spices. Still, it is crucial to provide precautions on ozone's effect on major active constituents before recommending this method for industrial application.

The Coumarin Derivative 5'-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways.

The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5'-hydroxy auraptene (5'-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5'-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5'-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5'-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5'-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5'-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5'-HA in BM cells. In conclusion, we identified 5'-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.

Antifungal and antihepatotoxic effects of sepia ink extract against oxidative stress as a risk factor of invasive pulmonary aspergillosis in neutropenic mice.

BACKGROUND: There is a great need for novel strategies to overcome the high mortality associated with invasive pulmonary aspergillosis (IPA) in immunocompromised patients. To evaluate the antifungal and antihepatotoxic potentials of Sepia ink extract, its effect on liver oxidative stress levels was analyzed against IPA in neutropenic mice using amphotercin B as a reference drug. MATERIALS AND METHODS: Eighty neutropenic infected mice were randomly assigned into four main groups. The 1(st) group was treated with saline, neutropenic infected (NI), the 2(nd) group was treated with ink extract (200 mg/kg) (IE) and the 3(rd) group was treated with amphotericin B (150 mg/kg) (AMB) and 4(th) group was treated with IE plus AMB. Treatment was started at 24 h after fungal inoculation (1×10(9) conidia/ml). RESULTS: The present study revealed good in vitro and in vivo antifungal activity of IE against A. fumigatus. IE significantly reduced hepatic fungal burden and returns liver function and histology to normal levels. Compared with the untreated infected group, mice in the IE, AMB, and IE+ AMB groups had increased glutathione reduced (GSH) and superoxide dismutase (SOD) and significantly reduced malondialdehyde (MDA) levels at 24 and 72 h after inoculation with A. fumigatus conidia. CONCLUSION: It is then concluded that in combination with antifungal therapy (AMB), IE treatment can reduce hepatic fungal burden, alleviate hepatic granulomatous lesions and oxidative stress associated with IPA in neutropenic mice.