WHY AYURVEDA IS IMPORTANT IN TIMES OF CORONA?
WE HAVE HAD THE CURE, NOW IT IS TIME TO SERVE IT!
Chloroquine and hydroxychloroquine increase pH within intracellular vacuoles and alter processes such as protein degradation by acidic hydrolases in the lysosome, assembly of macromolecules in the endosomes, and posttranslation modification of proteins in the Golgi apparatus. It is proposed that the antirheumatic properties of these compounds results from their interference with "antigen processing" in macrophages and other antigen-presenting cells. Acidic cytoplasmic compartments are required for the antigenic protein to be digested and for the peptides to assemble with the alpha and beta chains of MHC class II proteins. As a result, antimalarials diminish the formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and result in down-regulation of the immune response against autoantigenic peptides. Because this mechanism differs from other antirheumatic drugs, antimalarials are well suited to complement these other compounds in combination drug therapy.
https://www.ncbi.nlm.nih.gov/pubmed/8278823
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(06)70361-9/fulltext
Chloroquine analog is a diprotic weak base. The unprotonated form of chloroquine diffuses spontaneously and rapidly across the membranes of cells and organelles to acidic cytoplasmic vesicles such as endosomes, lysosomes, or Golgi vesicles and thereby increases their pH (Al‐Bari 2015). On oral administration, the analog is readily absorbed and concentrated in tissues such as the liver, spleen, and kidney (Al‐Bari 2015)‐ where several fatal viruses harbored, replicated, and infected (Geisbert et al. 2003). In cellular levels of the tissues, chloroquine becomes highly concentrated in such acidic organelles leading to dysfunction of several enzymes, e.g. those required for proteolytic processing and post‐translational modification of viral proteins (Fig. 1) (Savarino et al. 2003; Marzi et al. 2012). Consequently, chloroquine analogs inhibit the production of several cytokines, chemokines or mediators, whose excessive appearance contributes the severity of viral infections. Therefore, the inhibition of endosomal acidification by chloroquine analogs may become a potential therapeutic strategy for viral infections and associated pathologies.
chloroquine analogs inhibit these viral entry and replication processes into the cytoplasm of susceptible cells and thereby abrogate their infections (Chiang et al. 1996; Savarino et al. 2003). Furthermore, the dysfunction of various enzymes e.g. glycosylating enzymes, glycosyltransferases caused by increased acidic pH and/or structural changes in the Golgi apparatus with hydroxychloroquine or by specific interaction with chloroquine, have been shown to suppress not only glycosylation of SARS‐ coronaviruses (Vincent et al. 2005; Savarino et al. 2006) but also that of the HIV‐1 gp120 envelope protein, resulting in structural changes in the gp120 glycoprotein, which in turn reduce the reactivity and infectivity of newly produced virions (Savarino et al. 2004; Naarding et al. 2007). Since the surface glycoproteins of filoviruses (Ebola and Marburg) involve in initiation of infection (Takada et al. 1997; Yang et al. 2000), and cytotoxicity (Yang et al. 2000), the inhibition of glycosylation by the analogs prevents the viral entries for a wide variety of host cells and leads to suppress their pathogenicity by producing of noninfectious or decreased infectivity viruses. This inhibited glycosylation will therefore allow time for the adaptive immune response to deal with the infection (Baize et al. 1999).
chloroquine analogs regulate immune activation in viral infection (e.g., HIV‐1) with other antiretroviral agents. The analogs reduce systemic T‐cell activation (Murray et al. 2010; Leroux‐Roels et al. 2014; Routy et al. 2014) and immune hyperactivation in HIV/AIDS (Savarino and Shytaj 2015). Thus, the analogs are beneficial for chronic HIV‐infected individuals. As an endosomal inhibitor, chloroquine blocks Toll‐like receptor (TLR) mediated activation of plasmacytoid dendritic cells (pDC), and myeloid differentiation primary response gene 88 (MyD88) signaling by the decrease in levels of the downstream signaling molecules, interleukin‐1 receptor associated kinase 4 (IRAK‐4) and IFN regulatory factor 7 (IRF‐7) and by the inhibition of IFN‐α synthesis (Martinson et al. 2014). In addition to suppress pDC activation, the analogs also block the negative modulators of T‐cells such as indoleamine 2,3‐dioxygenase (IDO) and programmed death ligand 1 (PDL‐1). Since TLR stimulation and production of IFN‐α by pDC contribute to immune activation, blocking the pathway using chloroquine analogs will interfere emerging viral pathogenesis (Martinson et al. 2014).
In addition to the well‐known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, ACE2. This may negatively affect the virus‐receptor binding and abrogate the infection. The IC50 of chloroquine for inhibition of SARS‐CoV in vitro (8.8 ± 1.2 μmol/L) is significantly lower than its cytostatic activity which approximates the plasma chloroquine concentrations reached during treatment of acute malaria. More interestingly, the suppressing effect is observed when the cells are treated with chloroquine either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage (Keyaerts et al. 2004; Vincent et al. 2005). There are screened a library of 348 FDA‐approved drugs for anti‐MERS‐CoV activity in cell culture and only four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) have been identified to inhibit the viral replication (50% effective concentrations, EC50 3–8 μmol/L). Although the protective activity of chloroquine (alone or in combination) remains to be assessed in animal models, these findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS‐CoV (De Wilde et al. 2014).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461643/
Mahameda is a vital ingredient of Ashtawarga group and numerous Ayurvedic formulations such as Chyawanprash, Vachadi Taila, Astavarga Churna, Chitrakadi Taila, Mahakalyan Ghrita, Mahamayura Ghrita, Mahapadma Taila, Jivaniya Ghrita, Brahini Gutika, Vajikaran Ghrita, Indrokta Rasayan, etc.[1] Due to extensive usage, the demand of Mahameda is progressively increasing which leads to large scale and indiscriminate collection of wild material and ultimately to scarcity of the authentic source. Currently, Mahameda comes under the category of endangered plants.[2,3]
Traditionally, Mahameda is known to be effective against emaciation, senility, pain, pyrexia, weakness, burning sensation, phthisis, and pulmonary affections and also has other significant effects such as tonic, galactagogue, emollient, aphrodisiac, insecticidal, and leishmanicidal.[2]
Rhizomes of Mahameda have been proven for anti-oxidant,[6] antispasmodic, antidiarrheal,[7] antipyretic,[8] tracheorelaxant, anti-inflammatory,[9] antimicrobial,[10] antinociceptive, diuretic,[11] and antimalarial potential.[12] Rhizomes of Mahameda are known to contain phytoconstituents such as lysine, serine, aspartic acid, threonine, diosgenin, β-sitosterol, sucrose, glucose,[1] micronutrients (Zn, Fe, Pb, Cu, Ni, Cd, Cr, Co, Sb and Mn), macronutrients (Na, Ca, and K), and essential life nutrients (proteins, fats, carbohydrates, and ascorbic acid).[13] Few compounds have been isolated from the rhizomes of P. verticillatum which include lectins,[14] 5-hydroxymethyl-2-furaldehyde,[12] diosgenin, santonin,[6] 2-hydroxybenzoic acid, and β-sitosterol.[9] The present study was designed to isolate and identify other important phytoconstituents of Mahameda, to assist as markers in identifying adulteration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052943/
