Antiviral and immunomodulatory activity of curcumin: A case for prophylactic therapy for COVID-19.

Coronavirus disease-19 (COVID-19), a devastating respiratory illness caused by SARS-associated coronavirus-2 (SARS-CoV-2), has already affected over 64 million people and caused 1.48 million deaths, just 12 months from the first diagnosis. COVID-19 patients develop serious complications, including severe pneumonia, acute respiratory distress syndrome (ARDS), and or multiorgan failure due to exaggerated host immune response following infection. Currently, drugs that were effective against SARS-CoV are being repurposed for SARS-CoV-2. During this public health emergency, food nutraceuticals could be promising prophylactic therapeutics for COVID-19. Curcumin, a bioactive compound in turmeric, exerts diverse pharmacological activities and is widely used in foods and traditional medicines. This review presents several lines of evidence, which suggest curcumin as a promising prophylactic, therapeutic candidate for COVID-19. First, curcumin exerts antiviral activity against many types of enveloped viruses, including SARS-CoV-2, by multiple mechanisms: direct interaction with viral membrane proteins; disruption of the viral envelope; inhibition of viral proteases; induce host antiviral responses. Second, curcumin protects from lethal pneumonia and ARDS via targeting NF-κB, inflammasome, IL-6 trans signal, and HMGB1 pathways. Third, curcumin is safe and well-tolerated in both healthy and diseased human subjects. In conclusion, accumulated evidence indicates that curcumin may be a potential prophylactic therapeutic for COVID-19 in the clinic and public health settings.

In vitro dissolution profile comparison of an anti-migraine combinational drug in dosage form.

A novel in vitro dissolution profile was developed for formulated drug in combinational form containing naproxen sodium (NAP) and sumatriptan succinate (SUMA). This study was performed to understand the dissolution of the drug in the physiological temperature and pH. Dissolution testing was performed using USP 29 type II testing apparatus rotating at 50 r/min, in 900 mL deaerated buffer (pH 1.2, 4.5 and 6.8) which was maintained at (37 +/- 0.5) degrees C. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Aceclofenac (ACE) was used as internal standard. SUMA, ACE and NAP were eluted at 4.8, 5.7 and 7.9 min, respectively. As expected for enteric coated immediate release (IR) tablets, the dissolution of NAP and SUMA was rapid and essentially complete within 2 h using phosphate buffer (pH 6.8). The comparison of the dissolution profiles was realized by model independent approach using a difference factor (f1), similarity factor (f2) and dissolution efficiency (DE). Statistical results showed the profiles were similar to the reference and the test products. Hence, this method demonstrated to be adequate for in vitro studies of NAP and SUMA in the combinational dosage form, since there is no official monograph, collaborating to the official codes.

Herbex-kid Inhibits Immediate Hypersensitivity Reactions in Mice and Rats.

Herbex-kid (HK), a polyherbal formulation was evaluated in various experimental allergic models of Type I hypersensitivity reactions. Compound 48/80 (C 48/80) has been shown to induce rat mesentery mast cell degranulation and HK (1.07, 10.75 and 107.5 mg ml(-1)) inhibited the mast cell degranulation in a dose dependent manner. HK (1.07, 10.75 and 107.5 mg kg(-1); p.o.) showed dose-dependent protection against C 48/80 induced systemic anaphylaxis in male Balb/C mice. In active anaphylaxis model, male Wistar rats orally administered with 10.75 and 107.5 mg kg(-1) of HK showed significant (P < 0.01) protection against mast cell degranulation, while in passive anaphylaxis model, only at 107.5 mg kg(-1) showed significant (P < 0.01) reduction in mast cell degranulation. HK at all dose levels was able to significantly decrease the time spent in nasal rubbing in Wistar rats sensitized to ovalbumin, while only at 107.5 mg kg(-1) it showed significant (P < 0.01) reduction in number of sneezes. In C 48/80-induced skin itch model, all dose levels of HK significantly (P < 0.001) decreased the time spent in itching and the number of itches. HK did not produce any significant inhibition in histamine induced contraction in guinea pig ileum. From the above findings we conclude that the HK possesses antiallergic activity mediated by reducing of the release mediators from mast cells and also by 5-HT antagonism without the involvement of histamine (H1) receptors.

Antioxidant and hepatoprotective activity of the methanol extract of Careya arborea bark in Ehrlich ascites carcinoma-bearing mice.

The methanol extract of Careya arborea bark (MECA) was tested for antioxidant and hepatoprotective activity in Ehrlich ascites carcinoma (EAC) tumor-bearing mice. Tumor control animals inoculated with EAC showed a significant alteration in the levels of antioxidant and hepatoprotective parameters. The extract treatment at 50, 100 and 200 mg/kg body weight doses given orally caused a significant reversal of these biochemical changes towards the normal in serum, liver and kidney when compared to tumor control animals indicating the potent antioxidant and hepatoprotective nature of the standardized extract.

Phyllanthus maderaspatensis, a dietary supplement for the amelioration of adriamycin-induced toxicity and oxidative stress in mice.

The effect of ethanol extract of Phyllanthus maderaspatensis (PME), a popular south Indian dietary supplement, was studied for its chemoprotective property on adriamycin (ADR)-induced toxicity and oxidative stress in mice. Adriamycin toxicity was evaluated biochemically by measuring the serum concentration of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK). Genotoxicity was evaluated by measuring the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow cells. Oxidative stress in the heart tissue was estimated by measuring the glutathione (GSH) levels in the homogenate. The treatment of mice with different doses of PME (400 mg/kg and 600 mg/kg body weight, p.o.,) for 7 days before the administration of a single i.p. dose of ADR (15 mg/kg) exhibited significant protection in a dose-dependent manner. The results clearly indicate that PME has a protective effect against ADR-induced toxicity, as revealed by the decrease in the concentrations of LDH, CPK, and the frequency of MNPCEs. The increased levels of GSH are indicative of the antioxidant property of PME.

Hepatoprotective and antioxidant activity of methanol extract of Ficus glomerata.

The present study was carried out to evaluate Ficus glomerata extracts for antioxidant and hepatoprotective properties. The methanol extract of the bark of F. glomerata showed potent in vitro antioxidant activity when compared to the root methanol extract. In the in vivo studies, the CCl(4) treated control rats showed a significant alteration in the levels of antioxidant and hepatoprotective parameters. The methanol extract of the bark when given orally along with CCl(4) at the doses of 250 and 500 mg/kg body weight showed a significant reversal of these biochemical changes towards the normal when compared to CCl(4)-treated control rats in serum, liver and kidney. The results were comparable to those observed for standard sylimarin. Histological studies also confirmed the same. The results indicated the potent hepatoprotective and antioxidant nature of the bark extract.

In vitro antioxidant activity of Argyreia cymosa bark extracts.

The Argyreia cymosa bark extracts were subjected to in vitro antioxidant activity with different methods. The petroleum ether extract has shown antioxidant activity in ABTS, nitric oxide, hydroxyl radical (by p-NDA) and lipid peroxidation methods. The ethyl acetate extract has shown antioxidant activity in DPPH, H(2)O(2) and hydroxyl radical (by deoxyribose) scavenging methods.

The cytotoxic activity of the total alkaloids isolated from different parts of Solanum pseudocapsicum.

The total alkaloid fractions of the methanolic extracts of the leaves, ripe fruits, roots, seeds and stem of Solanum pseudocapsicum were subjected to in-vitro cytotoxicity, short-term toxicity and long-term survival studies. All the five fractions exhibited potent activity. The total alkaloid fraction of leaves was found to be the most potent. The HT-29 cell line was the most sensitive to the fractions. The cytotoxic concentration (CTC(50)) values for all these fractions ranged between 0.39-0.91, 0.68-2.8, 0.92-3.56, 4.05-8.2, 3.28-5.65 and 0.95-5.55 microg/ml, respectively for HT-29, RD-228, A-549, HEp-2, B(16)F(10) and Vero cell lines. In short-term toxicity studies, the fractions showed 50% viability at 93-128 microg/ml for DLA cells and 141-189 microg/ml for human lymphocytes. In the long-term survival studies on the cell lines RD-228, HEp-2 and Vero, cells retained their regenerative capacities at concentrations below 8 microg/ml. The total alkaloids of the plant, especially from the leaves merit further investigations to identify the active constituents in animal models.

Antioxidant activity of Caesalpinia sappan heartwood.

Antioxidant activity of Caesalpinia sappan heartwood was studied both by in vitro and in vivo models. The ethyl acetate, methanol and water extracts exhibited strong antioxidant activity as evidenced by the low IC50 values in both 1,1-diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide methods. The values were found to be less or comparable to those of ascorbic acid and rutin, the standards used. Administration of the successive methanol and water extracts at 50 and 100 mg/kg body weight given for four days prior to carbon tetrachloride (CCl4) treatment caused a significant increase in the level of superoxide dismutase (SOD) and catalase and a significant decrease in the level of thiobarbituric acid reactive substances (TBARS), when compared to CCl4 treated control in both liver and kidney. These changes observed at 100 mg/kg body weight treatment were comparable to those observed for standard vitamin E at 50 mg/kg treatment. The results support significant antioxidant nature of Caesalpinia sappan heartwood extracts.