The Pivotal Potentials of Scorpion Buthus Martensii Karsch-Analgesic-Antitumor Peptide in Pain Management and Cancer

Scorpion Buthus martensii Karsch -analgesic-antitumor peptide (BmK AGAP) has been used to treat diseases like tetanus, tuberculosis, apoplexy, epilepsy, spasm, migraine headaches, rheumatic pain, and cancer in China. AGAP is a distinctive long-chain scorpion toxin with a molecular mass of 7142 Da and composed of 66 amino acids cross-linked by four disulfide bridges. Voltage-gated sodium channels (VGSCs) are present in excitable membranes and partakes in essential roles in action potentials generation as compared to the significant function of voltage-gated calcium channels (VGCCs). A total of nine genes (Nav1.1–Nav1.9) have been recognized to encode practical sodium channel isoforms. Nav1.3, Nav1.7, Nav1.8, and Nav1.9 have been recognized as potential targets for analgesics. Nav1.8 and Nav1.9 are associated with nociception initiated by inflammation signals in the neuronal pain pathway, while Nav1.8 is fundamental for neuropathic pain at low temperatures. AGAP has a sturdy inhibitory influence on both viscera and soma pain. AGAP potentiates the effects of MAPK inhibitors on neuropathic as well as inflammation-associated pain. AGAP downregulates the secretion of phosphorylated p38, phosphorylated JNK, and phosphorylated ERK 1/2 in vitro. AGAP has an analgesic activity which may be an effective therapeutic agent for pain management because of its downregulation of PTX3 via NF-κB and Wnt/beta-catenin signaling pathway. In cancers like colon cancer, breast cancer, lymphoma, and glioma, rAGAP was capable of blocking the proliferation. Thus, AGAP is a promising therapy for these tumors. Nevertheless, research is needed with other tumors

Elucidating the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Chloroquine and Hydroxychloroquine

Chloroquine (CQ) and hydroxychloroquine (HCQ) are derivatives of 4-aminoquinoline compounds with over 60 years of safe clinical usage. CQ and HCQ are able to inhibit the production of cytokines such as interleukin- (IL-) 1, IL-2, IL-6, IL-17, and IL-22. Also, CQ and HCQ inhibit the production of interferon- (IFN-) α and IFN-γ and/or tumor necrotizing factor- (TNF-) α. Furthermore, CQ blocks the production of prostaglandins (PGs) in the intact cell by inhibiting substrate accessibility of arachidonic acid necessary for the production of PGs. Moreover, CQ affects the stability between T-helper cell (Th) 1 and Th2 cytokine secretion by augmenting IL-10 production in peripheral blood mononuclear cells (PBMCs). Additionally, CQ is capable of blocking lipopolysaccharide- (LPS-) triggered stimulation of extracellular signal-modulated extracellular signal-regulated kinases 1/2 in human PBMCs. HCQ at clinical levels effectively blocks CpG-triggered class-switched memory B-cells from differentiating into plasmablasts as well as producing IgG. Also, HCQ inhibits cytokine generation from all the B-cell subsets. IgM memory B-cells exhibits the utmost cytokine production. Nevertheless, CQ triggers the production of reactive oxygen species. A rare, but serious, side effect of CQ or HCQ in nondiabetic patients is hypoglycaemia. Thus, in critically ill patients, CQ and HCQ are most likely to deplete all the energy stores of the body leaving the patient very weak and sicker. We advocate that, during clinical usage of CQ and HCQ in critically ill patients, it is very essential to strengthen the CQ or HCQ with glucose infusion. CQ and HCQ are thus potential inhibitors of the COVID-19 cytokine storm