Russell's viper venom induced nephrotoxicity, myotoxicity, and hepatotoxicity­Neutralization with gold nanoparticle conjugated 2-hydroxy-4-methoxy benzoic acid in vivo.

Snakebite is one of the major neglected tropical diseases and health hazard that leads to significant mortality, particularly in rural populations of tropical and subtropical countries including India. Antisnake venom serum (ASVS) is the only specific treatment against snake envenomation. Available treatment i.e. ASVS have many limitations not only low efficiency but also considerable side effects. Search for alternative ASVS is a major domain in toxinology research. Targeted drug therapy using nanoparticles, an emerging area of nanotechnology, is one such alternative. Here, we studied neutralization of ing Russell's viper venom (RVV) induced toxicity (nephrotoxicity, myotoxicity, hepatotoxicity) with gold nanoparticle-conjugated 2-hydroxy-4-methoxy benzoic acid (GNP-HMBA) in male albino mice. We conjugated 2-hydroxy-4-methoxy benzoic acid (HMBA) with gold nanoparticle (GNP) by adsorption method, and physico-chemical characterization were done by DLS, ZETA potential, FTIR and TEM. Swiss male albino mice were divided into four groups viz., sham control, venom control, HMBA treated and GNP-HMBA treated. Each group had four mice (n=4). RVV was injected in all groups except sham control. Groups 3 and 4 had treatment with HMBA and GNP-HMBA, respectively. After 24 h, blood and urine were collected. Serum LDH, CK, SGPT, SGOT, γ-GT, ACP, ALP, urea, creatinine and urinary calcium and urinary phosphorus were measured. The hydrodynamic diameter of GNP-HMBA was 65-75 nm and TEM diameter was 18-28 nm. The serum/urine parameters were found significantly increased in venom control group. Degree of RVV neutralization was GNP-HMBA > HMBA. Treatment with GNP-HMBA showed partial protection of histopathological changes in RVV-induced kidney and liver tissues. It may be concluded that GNP-HMBA neutralized RVV-induced toxicities (nephrotoxicity, myotoxicity and hepatotoxicity) in male albino mice. Further studies are warranted in the development of alternative herbal-nanoparticle antidote against snake venom induced toxicity. Page(s): 7-14

Capsaicin Inhibits Shigella flexneri Intracellular Growth by Inducing Autophagy.

Antibiotic treatment plays an essential role in preventing Shigella infection. However, incidences of global rise in antibiotic resistance create a major challenge to treat bacterial infection. In this context, there is an urgent need for newer approaches to reduce S. flexneri burden. This study largely focuses on the role of the herbal compound capsaicin (Caps) in inhibiting S. flexneri growth and evaluating the molecular mechanism behind bacterial clearance. Here, we show for the first time that Caps inhibits intracellular S. flexneri growth by inducing autophagy. Activation of autophagy by Caps is mediated through transcription factor TFEB, a master regulator of autophagosome biogenesis. Caps induced the nuclear localization of TFEB. Activation of TFEB further induces the gene transcription of autophagosomal genes. Our findings revealed that the inhibition of autophagy by silencing TFEB and Atg5 induces bacterial growth. Hence, Caps-induced autophagy is one of the key factors responsible for bacterial clearance. Moreover, Caps restricted the intracellular proliferation of S. flexneri-resistant strain. The efficacy of Caps in reducing S. flexneri growth was confirmed by an animal model. This study showed for the first time that S. flexneri infection can be inhibited by inducing autophagy. Overall observations suggest that Caps activates TFEB to induce autophagy and thereby combat S. flexneri infection.

Capsaicin Inhibits Inflammation and Gastric Damage during H pylori Infection by Targeting NF-kB-miRNA Axis.

Helicobacter pylori (H. pylori) infection is considered as one of the strongest risk factors for gastric disorders. Infection triggers several host pathways to elicit inflammation, which further proceeds towards gastric complications. The NF-kB pathway plays a central role in the upregulation of the pro-inflammatory cytokines during infection. It also regulates the transcriptional network of several inflammatory cytokine genes. Hence, targeting NF-kB could be an important strategy to reduce pathogenesis. Moreover, treatment of H. pylori needs attention as current therapeutics lack efficacy due to antibiotic resistance, highlighting the need for alternative therapeutic approaches. In this study, we investigated the effects of capsaicin, a known NF-kB inhibitor in reducing inflammation and gastric complications during H. pylori infection. We observed that capsaicin reduced NF-kB activation and upregulation of cytokine genes in an in vivo mice model. Moreover, it affected NF-kB-miRNA interplay to repress inflammation and gastric damages. Capsaicin reduced the expression level of mir21 and mir223 along with the pro-inflammatory cytokines. The repression of miRNA further affected downstream targets such as e-cadherin and Akt. Our data represent the first evidence that treatment with capsaicin inhibits inflammation and induces antimicrobial activity during H. pylori infection. This alternative approach might open a new avenue in treating H. pylori infection, thus reducing gastric problems.

Anti-osteoarthritic activity of Bungarus fasciatus venom fraction BF-F47 involving molecular markers in the rats.

A heat stable protein BF-F47 was purified from the crude venom of Bungarus fasciatus by CM cellulose ion exchange chromatography and HPLC. Osteoarthritis (OA) was developed in male albino Wistar rats by collagenase injection. BF-F47 treatment significantly restored urinary hydroxyproline and glucosamine in OA rats. Serum acid phosphatase, alkaline phosphatase, creatinine and serum molecular markers TNF-α, IL-1ß, IL-17, cytokine induced neutrophil chemoattractant-1, matrix metalloproteinase-1, cathepsin-K, osteocalcin and PGE2 were also significantly altered. BF-F47 showed partial restoration of osteoarthritis joints. Thus, BF-F47 induced anti-osteoarthritic activity in Wistar rats acted through molecular markers of arthritis and inflammation.