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.

Kabasura Kudineer (KSK), a poly-herbal Siddha medicine, reduced SARS-CoV-2 viral load in asymptomatic COVID-19 individuals as compared to vitamin C and zinc supplementation: findings from a prospective, exploratory, open-labeled, comparative, randomized controlled trial, Tamil Nadu, India.

INTRODUCTION: Despite several ongoing efforts in biomedicine and traditional medicine, there are no drugs or vaccines for coronavirus disease 2019 (COVID-19) as of May 2020; Kabasura Kudineer (KSK), a polyherbal formulation from India's Siddha system of medicine, has been traditionally used for clinical presentations similar to that of COVID-19. We explored the efficacy of KSK in reducing viral load and preventing the disease progression in asymptomatic, COVID-19 cases. METHODS: A prospective, single-center, open-labeled, randomized, controlled trial was conducted in a COVID Care Centre in Chennai, India. We recruited reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 of 18 to 55 years of age, without clinical symptoms and co-morbidities. They were randomized (1:1 ratio) to KSK (60 mL twice daily for 7 days) or standard of care (7 days supplementation of vitamin C 60,000 IU morning daily and zinc 100 mg evening daily) groups. The primary outcomes were reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR], prevention of progression of asymptomatic to symptomatic state, and changes in the immunity markers including interleukins (IL-6, IL-10, IL-2), interferon gamma (IFNγ), and tumor necrosis factor (TNF α). Siddha clinical assessment and the occurrence of adverse effects were documented as secondary outcomes. Paired t-test was used in statistical analysis. RESULTS: Viral load in terms of the CT value (RdRp: 95% CI = 1.89 to 5.74) declined significantly on the seventh day in the KSK group and that of the control group, more pronounced in the study group. None progressed to the symptomatic state. There was no significant difference in the biochemical parameters. We did not observe any changes in the Siddha-based clinical examination and adverse events in both groups. CONCLUSION: KSK significantly reduced SARS-CoV-2 viral load among asymptomatic COVID-19 cases and did not record any adverse effect, indicating the use of KSK in the strategy against COVID-19. Larger, multi-centric trials can strengthen the current findings. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI2020/05/025215 . Registered on 16 May 2020.

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Design and synthesis of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones as a new class of H1-antihistaminic agents.

A series of novel 2-(3-substituted propyl)-3-(2-methyl phenyl) quinazolin-4-(3H)-ones were synthesized by the reaction of 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one with various amines. The starting material, 2-(3-bromopropyl thio)-3-(2-methyl phenyl) quinazolin-4-(3H)-one was synthesized from 2-methyl aniline. When tested for their in vivo H(1)-antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine induced bronchospasm significantly. Compound 2-(3-(4-methylpiperazin-1-yl) propylthio)-3-(2-methyl phenyl) quinazolin-4(3H)-one (OT5) emerged as the most active compound (71.70% protection) of the series when compared to the reference standard chlorpheniramine maleate (70.09% protection). Compound OT5 shows negligible sedation (7%) compared to chlorpheniramine maleate (33%). Therefore, compound OT5 can serve as the leading molecule for further development into a new class of H(1)-antihistaminic agents.

Neuroprotective potential of ethanolic extract of Pseudarthria viscida (L) Wight and Arn against beta-amyloid(25-35)-induced amnesia in mice.

The neuroprotective potential of ethanolic extract of roots of Pseudarthria viscida (L) Wight and Arn (EEPV) was investigated against beta-amyloid(25-35)-induced amnesia in mice which is a suitable animal model for Alzheimer's disease (AD). The senile plaques of beta-amyloid (Abeta) are major constituents accumulated during the progression of AD as a potent neurotoxicant. In our investigation, intracerebroventricular injection of Abeta(25-35) in mice induced the neurodegeneration, exhibited the increased time of escape latency in behavioral pattern using water maze and decreased the levels of antioxidants namley superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and vitamin C with elevated level of acetylcholinesterase enzyme (AChE). The neuroprotective potential of EEPV was determined by behavioral pattern using water maze and biochemical parameters such as SOD, CAT and GPx and vitamin C content as well as AChE. Mice were treated with EEPV at 200 and 400 mg/kg doses for 21 days. Except control, all animals received a single injection of neurotoxicant Abeta(25-35) on 14th day. In behavioural assessment, treatment with ethanolic extract improved the cognitive function in the water maze and attenuated the elevated levels of AChE with increase in antioxidant enzymes, indicating the neuroprotection with increased levels of vitamin C. These findings suggest that ethanolic extract of P. viscida exerts anti-amnesiac effects and enhances cognitive function.

Synthesis and spectral characterization of a new class of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-ones: antimicrobial, analgesic and antipyretic studies.

A series of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-ones (13c-21c) were synthesized by the base catalyzed nucleophilic substitution of N-chloroacetyl-2,6-diarylpiperidin-4-ones obtained from their corresponding 2,6-diarylpiperidin-4-ones with N-methylpiperazine. These newly synthesized compounds were characterized by one- and two-dimensional NMR spectral studies. In all the cases, the piperazine ring adopted normal chair conformation with equatorial orientation of methyl group irrespective of the non-chair conformations of the piperidin-4-one moiety. All the compounds were screened for their possible antibacterial and antifungal activities against a spectrum of microbial agents besides analgesic and antipyretic activities. These biological studies proved that compounds 17c/18c against bacterial and 18c/20c against fungal strains exhibited promising antimicrobial activities whereas 17c/19c and 18c/19c showed beneficial analgesic and antipyretic profiles, respectively, at a concentration of 60mg/kg and were also found to be more potent than the reference drug.