Immunomodulatory effect of Unani polyherbal formulation - Tiryaq Wabai in mild to moderate COVID-19 patients - A randomized placebo-controlled clinical trial.

BACKGROUND: The pathogenesis of COVID-19 includes an integrated immune-inflammatory response. Modulation of host immune responses against the SARS-CoV-2 virus might be effective therapeutic management. Various Unani formulations have an immunomodulatory effect. OBJECTIVE: To explore the immunomodulatory effect and safety of Unani polyherbal drug (Tiryaq Wabai) in COVID-19 patients. MATERIALS AND METHODS: The current study was a randomized placebo-controlled clinical trial that included 92 mild to moderate COVID-19 patients randomized into two groups. The Unani formulation Tiryaq Wabai (2 gm orally once a day) was used as an intervention for 45 days, while the control group received a placebo. Both groups received standard care treatment. The primary outcome was 50% increment in absolute lymphocyte count (ALC). The secondary outcome was 50% increment in mean lymphocyte percentage, CD4 cells, and CD8 cell count. The mean increase in all the above parameters has also been studied. Relevant statistical tests were used to analyze the effect. RESULTS: A statistically significant improvement in a 50% increase in ALC (p-value, 0.004), lymphocyte percentage (p-value, 0.056), CD4 (p-value, 0.005), and CD8 cell count (p-value, 0.050) was reported. Also, a significant improvement in the mean value of the lymphocyte percentage (p-value 0.0007), ALC (p-value 0.0022), CD4 cell count (p-value 0.0025), and CD8 cell count (p-value 0.0093) was observed after the treatment. One adverse event of mild grade was reported in the placebo group. The analysis of safety parameters (LFT and KFT) was normal for both groups. CONCLUSION: In mild to moderate COVID-19 patients, Tiryaq Wabai effectively showed immunomodulatory activity by improving ALC count, lymphocyte percentage, CD4, and CD8 cell count.

Ellagic acid protects type II collagen induced arthritis in rat via diminution of IKB phosphorylation and suppression IKB-NF-kB complex activation: in vivo and in silico study.

OBJECTIVE: The present study was designed to explore the potential anti-inflammatory and anti-arthritic effects of ellagic acid (EA) in collagen-induced arthritis (CIA). METHODS: CIA rats were treated with MTX (0.25 mg/kg body wt.) and EA (50 mg/kg b.wt.) for a period of 20 days. The effects of treatment in the rats were assessed biochemically by analyzing inflammatory mediators (NF-kB, iNOS, TNF-α, IL-1ß, IL-6 and IL-10) and oxidative stress related parameters (MPO, NO, LPO, catalase, SOD, GSH). In addition, we also assessed the expression of some inflammatory mediators TNF-α, CD8 + though immunohistochemistry in the joint tissue. RESULTS: In the present study, we found expression and synthesis of transcription factor NF-kB was prominent in CIA rats. In addition, main pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and the anti-inflammatory IL-10, was also stand out. Further, reactive oxygen/nitrogen species was also elevated in CIA rats. Treatment with EA ameliorates all the above mentioned inflammatory and oxidative stress related parameters to near normal. Further, we also confirmed the expression of TNF-α, CD8+ T cells through immunohistochemistry was mitigates in joint tissue of EA treated rats. We find EA significantly inhibited the developmental phase of arthritis. CONCLUSION: These results suggest that EA act as potent anti-arthritic and anti-inflammatory agent that could be used as a tool for the development of new drug for the treatment of arthritis.

Role of herbal medicines in the management of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The management of the worldwide spreading COVID-19 consists of amelioration of its symptoms but no cure is yet available. Herbal medicines supplemented with the Western medicine have been applied for COVID-19 treatment in India, China, Iran, and other countries. This systematic review and meta-analysis of RCTs evaluates the effect and safety of herbal intervention in the management of COVID-19. EXPERIMENTAL PROCEDURE: RCTs from databases like PubMed, Cochrane Library, ScienceDirect, Google Scholar, Science Direct, CTRI, AYUSH Research Portal, India, were reviewed and the data were extracted for study sample demographics, intervention details, clinical effect, inflammatory markers and safety monitoring. Outcomes were expressed as Risk-ratio (RR) with 95% CI for dichotomous data, and Mean-Difference (MD) with 95% CI for continuous data. RESULT AND CONCLUSION: From the 32 eligible studies, a total of 3177 COVID-19 patients were included in the review. Herbal intervention as an adjuvant to Western medicine causes significantly higher improvement compared to Western medicine alone [Fever (RR = 1.09 CI 1.03, 1.15), Cough (Risk-Ratio = 1.22 CI 1.08, 1.37), Fatigue (Risk-Ratio = 1.27 CI 1.11, 1.44), Chest CT Improvement (Risk-Ratio = 1.15 CI 1.08, 1.23)]. The laboratory parameters were also better in the herbal medicine group compared to standard care group only WBC (MD = 0.36 CI 0.16, 0.55), Lymphocyte percentage (MD = 5.48 CI 3.05, 7.92), Absolute lymphocyte count (MD = 0.23 CI 0.07, 0.39), CRP (MD = -5.66 CI -7.96, -3.37). However, duration of hospital stays (MD = -1.82 CI -3.84, 0.21); IL-6 (MD = -3.67 CI -8.76, 1.43), ESR Level (MD = -10.38 CI -25.96, 5.21) were statistically insignificant. No significant adverse events for herbal medications were noted in the included RCTs, during the time of the studies. (n = 665, RR 0.93; 95% CI 0.76, 1.14).

Concentration-dependent antagonistic persuasion of SDS and naphthalene derivatives on the fibrillation of stem bromelain.

Sodium dodecyl sulfate, a biological membrane mimetic, can be used to study the conversion of globular proteins into amyloid fibrils in vitro. Using multiple approaches, the effect of SDS was examined on stem bromelain (SB), a widely recognized therapeutic protein. SB is known to exist as a partially folded intermediate at pH 2.0, situation also encountered in the gastrointestinal tract (its site of absorption). In the presence of sub-micellar SDS concentration (500-1000 µM), this intermediate was found to exhibit great propensity to form large-sized ß-sheeted aggregates with fibrillar morphology, the hall marks of amyloid structure. We also observed inhibition of fibrillation by two naphthalene-based compounds, ANS and bis-ANS. While bis-ANS significantly inhibited fibril formation at 50 µM, ANS did so at relatively higher concentration (400 µM). Alcohols, but not salts, were found to weaken the inhibitory action of these compounds suggesting the possible involvement of hydrophobic interactions in their binding to protein. Besides, isothermal titration calorimetry and molecular docking studies suggested that inhibition of fibrillation by these naphthalene derivatives is mediated not just through hydrophobic forces, but also by disruption of π-π interactions between the aromatic residues together with the inter-polypeptide chain repulsion among negatively charged ANS/bis-ANS bound SB.