Zinc oxide nano-flowers improve the growth and propagation of mulberry cuttings grown under different irrigation regimes by mitigating drought-related complications and enhancing zinc uptake.

Silkworm larvae mainly consume mulberry leaves; therefore, mulberry cultivation is important for the production of raw silk. Drought stress and micronutrient deficiency (Zn) are known to affect the propagation of mulberry cuttings. In this purview, the current investigation attempted to inspect the efficacy of different concentrations of zinc oxide nano-flower (ZnNFs) applied through both soil admixture and foliar spray on the propagation of mulberry cuttings grown under deficit irrigation regimes. The overall results demonstrated that the ZnNF-treated plant cuttings were well-adapted to drought stress and performed better in comparison to the control set. Out of the tested concentrations - ZnNF-10 (applied as 10 mg/kg soil and 10 ppm as foliar spray thrice) was found to be optimum, showing relatively better initial root establishment, the emergence of leaves, and survival and sprouting percentage. Further studies also confirmed an improvement in the accumulation of photosynthetic pigments, carbohydrates, and protein content even under extreme drought conditions. Most importantly, the ZnNF-10 treatment contributed to ROS detoxification and cell membrane protection by enhancing the pool of antioxidant enzymes. The study further demonstrated that ZnNF-10 application enhanced zinc content by 147.50%, 179.49%, and 171.99% in root, shoot, and leaves of the treated cuttings; thereby, improving the bioaccumulation factor of the plant parts. All of these interactive phenomena led to an increment in shoot height, biomass, leaf area, and leaf number of cuttings. These findings, therefore, indicated that ZnNFs can be developed as a promising nano-fertilizer for mulberry growth facilitating Zn uptake and mitigation of drought-induced complications.

Alternanthera brasiliana L. extract alleviates carbon tetrachloride-induced liver injury and fibrotic changes in mice: Role of matrix metalloproteinases and TGF-ß/Smad axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alternanthera brasiliana L. is a flowering plant belonging to the family Amaranthaceae and is popularly known as "penicillin". It is used in folk medicine to treat infections, coughs, wound healing, and inflammatory diseases. AIM OF THE STUDY: We investigated the effect of Alternanthera brasiliana L. leaves hydroalcoholic extract (AB) against oxidative stress, inflammation, and fibrotic changes in an experimental model of carbon tetrachloride (CCl4)-induced liver injury and fibrosis in mice. MATERIALS AND METHODS: Thirty-six male Balb/C mice were randomized into five groups: normal control, AB control, CCl4 control, CCl4 + AB-200 mg/kg, and CCl4 + AB-400 mg/kg. In mice, liver injury was induced by intraperitoneal injection of CCl4 (20% in corn oil, 5 ml/kg body weight) thrice a week for six consecutive weeks. AB extract at two doses (200 mg/kg and 400 mg/kg body weight) was administered orally for six consecutive weeks. Liver injury-related serum markers (ALT, AST, ALP), antioxidants (GSH, GST, SOD, and vitamin C), pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-18, ultrasonographic and histological alterations, proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), nuclear factor-κB (p65) (NF-κB), nod-like receptor protein 3 (NLRP3), and TGF-ß/Smad signaling were accessed. LC-Q-TOF-MS/MS analysis of AB was performed. RESULTS: AB treatment significantly decreased the CCl4-induced rise in serum ALT, AST, and ALP activities and improved the histological alterations. Compared with the CCl4-treated group, treatment with AB significantly restored the hepatic antioxidants and reduced the pro-inflammatory cytokines in the liver. The antioxidant activity of AB may be attributed to its terpenoid constituents, which was confirmed by LC-Q-TOF-MS/MS analysis. The CCl4-induced rise in expression of MMP-2 and MMP-9 and decrease in TIMP-1 were markedly restored in the AB-treated groups. Further findings revealed a significant reduction in the protein levels of phospho-NF-κB (p65), NLRP3, TGF-ß, pSmad2/3, collagen I, and α-smooth muscle actin (α-SMA) in the AB treatment groups. CONCLUSIONS: The hepatoprotective effect of AB may be attributed to the high content of terpenoid compounds and alleviates liver injury and associated fibrotic changes through modulating MMPs, NF-κB (p65), and the TGF-ß/Smad axis.

Biological Activities, Pharmacokinetics and Toxicity of Nootkatone: A Review.

Plant-based drugs have a significant impact on modern therapeutics due to their vast array of pharmacological activities. The integration of herbal plants in the current healthcare system has emerged as a new field of research. It can be used for the identification of novel lead compound candidates for future drug development. Nootkatone is a sesquiterpene derivative and an isolate of grapefruit. Shreds of evidence illustrate that nootkatone targets few molecular mechanisms to exhibit its pharmacological activity and yet needs more exploration. The current review is related to nootkatone, drafted through a literature search using research articles and books from different sources, including Science Direct, Google Scholar, Elsevier, PubMed, and Scopus. It has been reported to possess a wide range of pharmacological activities such as anti-inflammatory, anticancer, antibacterial, hepatoprotective, neuroprotective, and cardioprotective. Although preclinical studies in experimental animal models suggest that nootkatone has therapeutic potential, it is further warranted to evaluate its toxicity and pharmacokinetic parameters before being applied to humans. Hence, in the present review, we have summarized the scientific knowledge on nootkatone with a particular emphasis on its pharmacological properties to encourage researchers for further exploration in preclinical and clinical settings.

Toll-like receptor 4: An attractive therapeutic target for acute kidney injury.

Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.

Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia.

Hydrogen sulfide (H(2)S) has recently been identified as a regulator of various physiological events, including vasodilation, angiogenesis, antiapoptotic, and cellular signaling. Endogenously, H(2)S is produced as a metabolite of homocysteine (Hcy) by cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST). Although Hcy is recognized as vascular risk factor at an elevated level [hyperhomocysteinemia (HHcy)] and contributes to vascular injury leading to renovascular dysfunction, the exact mechanism is unclear. The goal of the current study was to investigate whether conversion of Hcy to H(2)S improves renovascular function. Ex vivo renal artery culture with CBS, CSE, and 3MST triple gene therapy generated more H(2)S in the presence of Hcy, and these arteries were more responsive to endothelial-dependent vasodilation compared with nontransfected arteries treated with high Hcy. Cross section of triple gene-delivered renal arteries immunostaining suggested increased expression of CD31 and VEGF and diminished expression of the antiangiogenic factor endostatin. In vitro endothelial cell culture demonstrated increased mitophagy during high levels of Hcy and was mitigated by triple gene delivery. Also, dephosphorylated Akt and phosphorylated FoxO3 in HHcy were reversed by H(2)S or triple gene delivery. Upregulated matrix metalloproteinases-13 and downregulated tissue inhibitor of metalloproteinase-1 in HHcy were normalized by overexpression of triple genes. Together, these results suggest that H(2)S plays a key role in renovasculopathy during HHcy and is mediated through Akt/FoxO3 pathways. We conclude that conversion of Hcy to H(2)S by CBS, CSE, or 3MST triple gene therapy improves renovascular function in HHcy.