miRNA-15/IL-10Rα axis promotes Kabasura Kudineer (Indian traditional Siddha formulation) induced immunomodulation by suppressing oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Kabasura Kudineer (KK), the traditional Indian medicine of Siddha, effectively manages common respiratory symptoms such as flu, cold, and fever. However, there is no evidence of the immunomodulatory capacity of KK in the cultured Jurkat T-lymphocytes under the LPS insult studied. AIM OF THE STUDY: Assess the effect of the traditional Indian medicine of Siddha, Kabasura Kudineer (KK) on immunomodulation by suppressing oxidative damage in cultured Jurkat T cells in vitro. The miRNA activity on anti-inflammatory gene receptors and cellular nitric oxide levels also was studied. MATERIALS AND METHODS: Jurkat T cells were exposed to LPS treatment in the presence or absence of KK. Cell viability and nitric oxide (NO) were measured with MTT and Griess assay. Cellular antioxidant systems (glutathione and SOD) were determined using glutathione and SOD assay. Lipid peroxidation was measured using an MDA assay. MiRNA-15a-5p expression was performed using microRNA qPCR Assays. Both inflammatory and anti-inflammatory genes (IL-6, IL-1, IL-10, IL-13) were performed using a qPCR and ELISA assay. RESULTS: The data showed that reduced cell proliferation and exaggerated NO production was observed in LPS treated condition compared to the control condition. Further, LPS treatment increased lipid peroxidation and reduced antioxidant enzyme activities (SOD and glutathione) in cultured Jurkat T cells. However, treatment with KK or N-acetyl cysteine (NAC; antioxidant) treatment mitigates the above effect. Mechanistically, LPS-induced oxidative stress upregulated miR- 15-5p expression and suppressed IL-10 Receptor alpha (IL-10Rα) by binding to its 3'-UTR region. The deregulated expression of IL-10Rα expression leads to increased IL-6 and IL-1ß expression in LPS-induced Jurkat T cells; however, treatment with KK or NAC reversed the above effects. CONCLUSION: Collectively, our study revealed the previously undefined mechanistic role of Kabasura Kudineer (KK) that alleviates the LPS-induced oxidative damage associated with inflammation by inhibiting the miRNA-15-5p/IL-10Rα axis.

Safety and efficacy of siddha medicine preparation in the management of COVID-19: A prospective randomised open label study.

Background: The use of complementary and alternative medicine (CAM) therapies has surged since the spread of COVID-19 pandemic. However, the efficacy and safety of these CAM therapies remains majorly unexplored. Objective: To understand the efficacy and safety of Nochi Kudineer Chooranam (5 gm), Mahasudarsan Chooranam (3 gm) , Adathodai Manapagu (10 ml), Omatheeneer (10 ml), Maldevi chenduram (100 mg) with honey in management of COVID 19 patients. Methods: We conducted a randomised, controlled, open label trial in patients hospitalized with SARS-CoV-2 infection who had an oxygen saturation of 90% or more while breathing ambient air. Patients were randomized into two groups in a 1:1 ratio to either intervention group, receiving seven days of siddha medicine (Intervention group; n = 50) or standard care (control group; n = 50). The primary end point was clinical markers and patient recovery status on day 8. Results: A total of 100 patients with confirmed COVID-19 with average age of 37 yrs (interquartile range, 28-49) participated in the study. There was no statistically difference between groups at baseline (P > 0.05). After intervention, patients in the intervention group had statistically (P < 0.05) significant reduction in the symptoms when compared to standard care. By end of the intervention period, 6 patients (12%) were hospitalized in the control group and none of them were reported for intervention group. Conclusion: Among patients with mild to moderate COVID-19, 7 days of siddha medicine showed a significant reduction in the clinical symptoms and requirement of hospitalisation, with no adverse events. Therefore, the particular siddha medicine preparation could be used safely and effectively for the management of COVID-19 patients.

Safety and efficacy of a Siddha Medicine fixed regimen for the treatment of asymptomatic and mild COVID-19 patients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive threat to public health worldwide. Siddha system of medicine is one of the traditional medicines of South India. The recommended formulations in Siddha Sasthric Medicines- Fixed Regimen (SSM-FiRe) are Amukkura tablets, Kaba Sura Kudineer (KSK) for asymptomatic COVID-19 positive (RT-PCR) patients, and Athimathuram tablets, Adathodai Manappagu syrup, Thippili Rasayanam, Brahmananda Bairavam tablet, and Notchi Kudineer for mild symptomatic patients. The core objective of the trial was to document the efficacy of SSM-FiRe in the prevention of asymptomatic and mild COVID-19 disease progression to the next level of severity, reduce the severity of symptoms and revert to RT-PCR Negative. Methods: An exploratory, prospective, open-labeled, single-arm, non-randomized trial was designed as per GCP guidelines to assess the efficacy of SSM-FiRe. Sixty RT-PCR positive participants who were asymptomatic or with mild COVID-19 symptoms were recruited for the study at the Siddha COVID Care Centre, Vyasarpadi, Chennai from June to August 2020. Nasal and oropharyngeal swab tests were performed on the 0, 7th, and 14th days. All participants were treated with SSM - FiRe regimen. All the participants were also assessed based on Siddha Yakkkaiyin Ilakkanam, which included Clinical symptoms and vitals. Laboratory investigations such as Haemogram, Liver Function Test, Renal Function Test, HbA1C, Electrolytes, Inflammatory markers, Cardiac profile, Immunoglobulins, and anti-SARS-CoV-2 antibody tests were performed. Results: 83% of COVID-19 patients turned RT-PCR negative on the 7th day and in most of the cases, symptoms were reduced within the first 5 days of admission. The RT-PCR cycle threshold (ct) value increased significantly (<0.001) after treatment and all the participants were RT-PCR negative, except one, who was positive even after 14 days. Anti-SARS-CoV-2 antibodies developed significantly (p-value - 0.006). LFT, RFT, CBC, Total proteins, and electrolytes continued to be in the normal range after treatment, indicating the safety of the intervention. Conclusion: Asymptomatic and mild COVID-19 disease can be well managed by SSM - FiRe treatment, Further studies could be taken up to strengthen the findings.