Investigation of The Effect of Metal-based Medicine Arsenicum album on Humoral Immune Response in SRBC-immunized Mice.

BACKGROUND: In complementary and alternative medicinal systems, the Arsenicum album in ultra-high dilution was used in various therapeutic conditions, considering its effects on the body's immune system, including the COVID-19 pandemic. However, scientific evidence regarding its immunomodulatory effects is insufficient. OBJECTIVE: The current study aimed to investigate the immunomodulatory effects of Arsenicum album in an experimental mouse model. MATERIALS AND METHODS: Immunomodulatory activity of potentized dilutions of Arsenicum album i.e., 6C, 30C, 200C in BALB/c mice was evaluated by humoral antibody titer and delayed- type hypersensitivity assays wherein a fixed concentration (0.5 ml of 1× 109 cells/ml) of freshly prepared sheep RBC was administered as a foreign antigen to generate primary and secondary antibodies. RESULTS: Arsenicum album showed significant immunomodulatory activity by increasing primary antibody titer evaluated on day 21 of the treatment in all the dilutions as compared to SRBC and vehicle control group in humoral immune response assay without showing any effect on delayed-type hypersensitivity. CONCLUSION: The results of this preliminary study indicate that oral administration of Arsenicum album has the potential to augment primary humoral response at all dilutions. Hence, the possibility of using the Arsenicum album could be explored to treat immunological conditions, infections, etc., as an alternative therapy alongwith modern medicines.

Randomised controlled trial to compare efficacy of standard care alone and in combination with homoeopathic treatment of moderate/severe COVID-19 cases.

BACKGROUND & OBJECTIVES: No definite treatment is known for COVID-19 till date. The objective of this study is to assess the efficacy of customized Homoeopathic medicines, when used as an add-on treatment to Standard of Care (SOC), in patients suffering from moderate to severe COVID-19 infection. METHODS: This was a randomized, controlled, single-blind, parallel-group trial where 214 COVID19-positive patients were screened for moderate and severe cases of COVID-19. Adjuvant homoeopathic medicines were given in the treatment group and SOC was given to both groups. The duration of oxygen support was compared as the primary outcome. Subjects were followed for 28 days or till the end-point of mechanical ventilation/ death. RESULTS: Of 129 subjects included, 57 and 55 were severe; and 8 and 9 were moderate cases in Homoeopathy and SOC arms, respectively. In all, 9 (15.2%) participants in Homoeopathy and 20 (32.2%) participants in SOC arms eventually expired (p<0.05). Oxygen support was required for 9.84±7.00 and 14.92±7.549 days in Homoeopathy and SOC arms, respectively (p<0.005). Subjects receiving Homoeopathy (12.9±6.days) had a shorter hospitalization stay than in SOC (14.9±7.5 days). Homoeopathy arm (10.6±5.7 days) also showed statistically significant mean conversion time of of Realtime-Polymerase Chain Reaction (RT-PCR) from positive to negative than the SOC arm (12.9±5.6 days). The mean score of Clinical Outcome Ordinal Scale (COOS) was lower in the Homoeopathy arm. Laboratory markers [Interleukins (IL)-6, C-reactive protein (CRP), Neutrophils-Lymphocytes ratio (NLR)]were normalized earlier in Homoeopathy arm. CONCLUSION: Homoeopathy, as add-on therapy with SOC for COVID-19 management, demonstrates a reduction in mortality and morbidity, by reduced requirement of oxygen and hospitalization. Some laboratory markers are normalized at an earlier time. Hence, there is overall control over the disease. Registry: The study was registered on the http://ctri.nic.in/Clinicaltrials website under identifier number: CTRI/2020/12/029668 on 9th December 2020.

Effectiveness of Eupatorium perfoliatum 30C in Prevention of Dengue Fever and Acute Febrile Illness during 2017 Dengue Outbreak in Urban Slums of Delhi: A Prospective, Open-Label, Community-Based, Parallel Cohort Study.

OBJECTIVE: This study was undertaken to assess the effectiveness of Eupatorium perfoliatum (EP) 30C on the incidence of dengue fever and acute febrile illness (AFI) during the 2017 dengue outbreak. METHODS: We conducted a prospective, open-label, community-based parallel cohort study involving apparently healthy individuals residing in 06 urban slums (JJ colony) of Delhi. The participants were enrolled in two cohorts - the medicine cohort (MC) and the control cohort (CC). Participants in MC were given weekly one dose of EP 30C for 10 weeks along with Information, Education and Communication (IEC) material regarding dengue. Participants in the CC were provided with the IEC material only. The primary outcome measure was the incidence of dengue fever as per case definitions notified in the national guidelines for clinical management of dengue fever by the Government of India during the 10 weeks follow-up period. The secondary outcome measures were the incidence of AFI and the hospitalization of confirmed dengue cases. RESULTS: The analysis included 40,769 participants residing in 06 slum clusters of Delhi out of which 28,321 participants were in MC and 12,448 participants were in CC. The incidence of laboratory-confirmed dengue in the MC was 2.57 per 10,000 person-weeks (95% confidence interval [CI], 2.02-3.22) in comparison with 7.55 per 10,000 person-weeks (95% CI, 6.12-9.21) in the CC. The incidence of AFI in the MC was 19.66 per 10,000 person-weeks (95% CI, 18.07-21.36) in comparison with 40.96 per 10,000 person-weeks (95% CI, 37.48-44.67) in the CC. The overall protective effect of EP against laboratory-confirmed dengue was 65.77% (95% CI, 53.37-74.87; p = 0.0001) and against AFI was 52.58% (95% CI, 46.37-58.07; p = 0.0001). Hospitalization reported in the MC was nil as against 4.35% in the CC. No dengue-related case fatalities were reported from either cohort. None of the participants from the MC reported any adverse events owing to the prophylactic intervention. CONCLUSION: The study concludes that EP 30C was able to prevent dengue significantly. Randomized controlled trials are needed to confirm or refute our findings.Das Ziel dieser Studie war die Beurteilung der Wirksamkeit von Eupatorium perfoliatum (EP) 30C auf die Inzidenz von Dengue-Fieber und akuter fiebriger Erkrankung (AFE) während des Dengue-Ausbruchs 2017.Wir führten eine prospektive, unverblindete, Bevölkerungs-Parallelgruppen-Kohortenstudie mit augenscheinlich gesunden Bewohnern von 6 städtischen Slums (JJ-Kolonie) in Delhi durch. Die Teilnehmer wurden in 2 Kohorten aufgenommen, einer Medizinkohorte (MK) und einer Kontrollkohorte (KK). Die Teilnehmer in der MK erhielten 10 Wochen lang wöchentlich eine Dosis EP 30C und dazu Aufklärungsmaterialien über Dengue. Die Teilnehmer in der KK erhielten nur die Aufklärungsmaterialien. Die primäre Zielgröße war die Dengue-Fieber-Inzidenz laut der in den nationalen Leitlinien für das klinische Management des Dengue-Fiebers von der indischen Regierung bekannt gegebenen Falldefinition in dem zehnwöchigen Beobachtungszeitraum. Die sekundären Zielgrößen waren die Inzidenz von AFE und die Anzahl hospitalisierter bestätigter Dengue-Fälle.In die Analyse wurden 40,769 Bewohner von 6 Slum-Clustern in Delhi einbezogen, davon wurden 28,321 Teilnehmer in die MK aufgenommen und 12,448 Teilnehmer in die KK. Die Inzidenz von im Labor bestätigter Dengue betrug in der MK 2,57 pro 10,000 Personen/Woche (95%-Konfidenzintervall [KI]: 2,02­3,22), verglichen mit 7,55 pro 10,000 Personen/Woche (95%-KI: 6,12­9,21) in der KK. Die Inzidenz von AFI betrug in der MK 19,66 pro 10,000 Personen/Woche (95%-Konfidenzintervall [KI]: 18,07­21,36), verglichen mit 40,96 pro 10,000 Personen/Woche (95%-KI: 37,48­44,67) in der KK. Der Schutzeffekt (SE) von EP betrug gegen im Labor bestätigte Dengue 65,77% (95%-KI: 53,37­74,87; p = 0,0001) und gegen AFI 52,58% (95%-KI: 46,37­58,07; p = 0,0001). Die Hospitalisierungsrate war in der MK gleich Null versus 4,35% in der KK. In keiner Kohorte waren Dengue-bedingte Todesfälle zu verzeichnen. Bei keinem der Teilnehmer in der MK traten jegliche unerwünschten Ereignisse infolge der prophylaktischen Maßnahme auf.Die Studie gelangt zu dem Schluss, dass Eupatorium perfoliatum 30C in signifikantem Maße Dengue vorbeugen konnte. Randomisierte kontrollierte Studien sind erforderlich, um unsere Ergebnisse zu bestätigen bzw. zu widerlegen.

Evaluation of Therapeutic Potential of Selected Plant-Derived Homeopathic Medicines for their Action against Cervical Cancer.

BACKGROUND: Plant-derived homeopathic medicines (HMs) are cheap and commercially available but are mechanistically less explored entities than conventional medicines. PURPOSE: The aim of our study was to evaluate the impact of selected plant-derived HMs derived from Berberis aquifolium (BA), Berberis vulgaris (BV), Mentha piperita (MP), Curcuma longa (CL), Cinchona officinalis (CO), Thuja occidentalis (TO) and Hydrastis canadensis (HC) on cervical cancer (CaCx) cells in vitro. METHODS: We screened the mother tincture (MT) and 30C potencies of the above-mentioned HMs for anti-proliferative and cytotoxic activity on human papillomavirus (HPV)-negative (C33a) and HPV-positive CaCx cells (SiHa and HeLa) by MTT assay. Total phenolic content (TPC) and the free-radical scavenging activity of each HM was also determined using standard assays. Phytochemicals reportedly available in these HMs were examined for their potential inhibitory action on HPV16 E6 by in silico molecular docking. RESULTS: All tested MTs induced a differential dose-dependent cytotoxic response that varied with cell line. For C33a cells, the order of response was TO > CL > BA > BV > HC > MP > CO, whereas for SiHa and HeLa cells the order was HC > MP > TO > CO > BA > BV > CL and CL > BA > CO, respectively. 30C potencies of all HMs showed an inconsistent response. Further, anti-CaCx responses displayed by MTs did not follow the order of an HM's phenolic content or free radical scavenging activity. Analysis revealed anti-oxidant content of BA, BV and HC had the lowest contribution to their anti-CaCx activity. Using in silico modeling of molecular docking between the HPV16 E6 protein crystallographic structures (6SJA and 4XR8) and main phytochemical components of BV, BA, HC, CL and TO, their potential to inhibit the HPV16 E6 protein carcinogenic interactions was identified. CONCLUSION: The study has shown a comparative evaluation of the potential of several plant-derived MTs and HMs to affect CaCx cell line survival in vitro (through cytotoxicity and free radical scavenging) and their theoretical molecular targets in silico for the first time. Data demonstrated that MTs of BA and BV are likely to be the most potent HMs that strongly inhibited CaCx growth and have a strong anti-HPV phytochemical constitution.

Impact of COVID-19 Pandemic on Patients with Non-Communicable Disease: An Observational Cross-Sectional Study at AYUSH Set-Ups of Krishna and Darjeeling District, India.

OBJECTIVE: The objective of this study was to determine the impact of COVID-19 in patients suffering from NCDs in terms of their knowledge, awareness, perception about COVID-19, use of AYUSH immune boosters (AIB), and management of chronic condition during the pandemic. METHOD: During the unlock down period (October 2020), a cross-sectional study was conducted in the Krishna and Darjeeling district of Andhra Pradesh and West Bengal, India. 499 individuals suffering from at least one chronic disease were interviewed using a structured questionnaire. Logistic regression was applied to investigate the relationship of socio-demographic characteristics, AIB, and morbidity with pandemic-related care challenges. Principal component analysis was applied to minimize the dimensionality of factors related to COVID care challenges. RESULTS: 499 individuals were surveyed. 91% identified at least three correct COVID appropriate behaviours. 92.2% considered the coronavirus to be a potential threat (mean ± SD: 5.8 ± 2.6). 44.7% and 55.3% lived with one and 2 or more chronic conditions, respectively. Hypertension alone (27.4%) and diabetes with hypertension (33%) were leading presentations. Out of 499, participants, 88.8% had at least one form of AIB. 52% took Ars. alb. with other AIB and 40% took Ars. alb. alone. Only 9 participants were infected with COVID-19. CONCLUSION: In the interest of a densely populated country like India, the inclusion of simple and safe AYUSH measures is realistic, ethical, and cost-effective. AYUSH interventions as COVID-19 prophylactic and treatment as well as integrative care of chronic illnesses such as NCDs are suggested.

Bibliography of Homeopathic Intervention Studies (HOMIS) in Human Diseases.

Objectives: Homeopathy (HOM) is a therapeutic method, which is widely used by patients and medical professionals. The medical conditions as well as the homeopathic medical products investigated vary strongly. There is an extensive amount of research, and this necessitates a bibliography that comprehensively presents the entire body of clinical evidence grouped according to medical conditions. Design: Thirty-seven online sources as well as print libraries were searched for HOM and related terms in eight languages (1980 to March 2021). We included studies that compared a homeopathic medicine or intervention with a control regarding the therapeutic or preventive outcome of a disease (classified according to International Classification of Diseases-10). The data were extracted independently by two reviewers and analyzed descriptively. Results: A total of 636 investigations met the inclusion criteria, of which 541 had a therapeutic and 95 a preventive purpose. Seventy-three percent were randomized controlled trials (n = 463), whereas the rest were non-randomized studies (n = 173). The leading comparator was placebo (n = 400). The type of homeopathic intervention was classified as multi-constituent or complex (n = 272), classical or individualized (n = 176), routine or clinical (n = 161) and isopathic (n = 19), or various (n = 8). The potencies ranged from 1X (dilution of -10,000) to 10 M (100-10.000). The included studies explored the effect of HOM in 223 medical indications. We present the evidence in an online database. Conclusions: This bibliography maps the status quo of clinical research in HOM. The data will serve for future targeted reviews, which may focus on the most studied conditions and/or homeopathic medicines, clinical impact, and the risk of bias of the included studies.

Efficacy of Arsenicum album 30C in the Prevention of COVID-19 in Individuals Residing in Containment Areas: A Prospective, Multicenter, Cluster-Randomized, Parallel-Arm, Community-Based, Open-Label Study.

OBJECTIVE: During the early part of the COVID-19 pandemic, non-pharmacologic interventions were the strategies for the prevention of severe acute respiratory syndrome coronavirus 2. The Ministry of Ayush, Govt. of India, had advised Arsenicum album 30C as a prophylactic to prevent COVID-19. This study was undertaken to evaluate the protective efficacy and safety of the Arsenicum album 30C. METHODS: We conducted a prospective, multicenter, cluster-randomized, parallel-arm, community-based, open-label study involving apparently healthy individuals residing in containment areas of 7 cities in India. Clusters are defined as the population residing in the containment areas, who are under restriction for movement. Forty-two clusters were randomly assigned at 2:1 to the Arsenicum album 30C group (30 clusters) or to the control group (12 clusters, which received no specific therapy). The medicine was given twice daily for 7 days. The primary outcome was the incidence of COVID-19, as per the case definition notified by the National Centre for Disease Control, Government of India, during 3-week follow-up period. RESULTS: The analysis included 32,186 individuals residing in 42 clusters (containment areas). A total of 22,693 individuals from 30 clusters received Arsenicum album 30C, and 9,493 individuals from 12 clusters were observed in the control group. The overall protective effect of the Arsenicum album 30C was 80.22% (95% confidence interval [CI], 71.16-86.44; 40 cases per 22,693 [6.04 per 10,000 person-weeks] in the Arsenicum album 30C group vs. 84 cases per 9,493 [29.78 per 10,000 person-weeks] in the control group). The protective effect of the Arsenicum album 30C against laboratory-confirmed COVID-19 was 68.22% (95% [CI], 49.64-80; 32 cases per 22,693 [4.83 per 10,000 person-weeks] in the Arsenicum album 30C group vs. 42 cases per 9,493 [14.93 per 10,000 person-weeks] in the control group). Adverse effects observed in both groups were mild and resolved without medication and sequelae. CONCLUSION: Homeopathic medicine Arsenicum album 30C was associated with a decrease in the incidence and provided some protection against COVID-19 as compared to nontreatment. Further randomized, double-blind, placebo-controlled trials may be conducted to validate the results of this study.In der Anfangszeit der COVID-19-Pandemie setzte man auf nicht-medikamentöse Massnahmen zur Prävention von Infektionen mit SARS-CoV-2 (Schweres-Akutes-Respiratorisches-Syndrom-Coronavirus 2). Das Ayush-Ministerium der indischen Regierung empfahl Arsenicum album 30C als Prophylaxe zur COVID-19-Prävention. Das Ziel dieser Studie war die Beurteilung der Schutzwirkung und Sicherheit von Arsenicum album 30C.An unserer prospektiven, multizentrischen, Cluster-randomisierten, unverblindeten Parallelgruppen-Bevölkerungs-Studie nahmen gesund erscheinende Bewohner von Sperrzonen in sieben indischen Städten teil. Die Cluster waren definiert als die Bewohnerpopulation je einer Sperrzone, für welche Mobilitätsbeschränkungen galten. 42 Cluster wurden per Randomisierung im Verhältnis 2:1 dem Arsenicum-album-30C-Arm (30 Cluster) oder dem Kontrollarm (12 Cluster, die keine spezifische Behandlung erhielten) zugeteilt. Das Medikament wurde sieben Tage lang zweimal täglich angewendet. Die primäre Zielgröße war die COVID-19-Inzidenz laut der vom National Centre for Disease Control der indischen Regierung bekannt gegebenen Falldefinition in einem Nachbeobachtungszeitraum von drei Wochen.Die Analyse umfasste 32.186 Personen in 42 Clustern (Sperrzonen). Insgesamt 22.693 Personen in 30 Clustern erhielten Arsenicum album 30C, und 9.493 Personen in 12 Clustern wurden als Kontrollarm beobachtet. Die Ergebnisse für Alter, Geschlecht und Komorbidität waren im Behandlungs- und Kontrollarm vergleichbar. Die Gesamt-Schutzwirkung von Arsenicum album 30C betrug 80,22 % (95-%-Konfidenzintervall [KI]: 71,16­86,44; 40 Fälle unter 22.693 [6,04 pro 10.000 Personen-Wochen] im Arsenicum-album-30C-Arm vs. 84 Fälle unter 9.493 [29,78 pro 10.000 Personen-Wochen] im Kontrollarm). Die Schutzwirkung von Arsenicum album 30C gegen laboranalytisch bestätigte COVID-19-Erkrankung betrug 68,22 % (95-%-KI: 49,64­80; 32 Fälle unter 22.693 [4,83 pro 10.000 Personen-Wochen] im Arsenicum-album-30C-Arm vs. 42 Fälle unter 9.493 [14,93 pro 10.000 Personen-Wochen] im Kontrollarm). Die beobachteten unerwünschten Wirkungen waren in beiden Gruppen von geringer Schwere und klangen ohne Medikation folgenlos ab.Das Homöopathikum Arsenicum album 30C war im Vergleich zur Nichtbehandlung mit einer Verringerung der Inzidenz assoziiert und bot gewissen Schutz vor COVID-19. Weitere randomisierte, doppelblinde, placebokontrollierte Studien könnten durchgeführt werden, um die Ergebnisse dieser Studie zu validieren.

Homeopathy as an Adjuvant to Standard Care in Moderate and Severe Cases of COVID-19: A Single-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVES: This study aimed to evaluate whether individualized homeopathic medicines have a greater adjunctive effect than adjunctive placebos in the treatment of moderate and severe cases of coronavirus disease 2019 (COVID-19). METHODS: The study was a randomized, single-blind, prospective, placebo-controlled clinical trial set in the clinical context of standard care. INTERVENTION: Patients of either sex, admitted in a tertiary care hospital, suffering from moderate or severe COVID-19 and above 18 years of age were included. In total, 150 patients were recruited and then randomly divided into two groups to receive either individualized homeopathic medicines or placebos, in addition to the standard treatment of COVID-19. OUTCOME MEASURES: The primary outcome was time taken to achieve RT-PCR-confirmed virus clearance for COVID-19. Secondary outcomes were changes in the Clinical Ordinal Outcomes Scale (COOS) of the World Health Organization, the patient-reported MYMOP2 scale, and several biochemical parameters. Parametric data were analyzed using unpaired t-test. Non-parametric data were analyzed using the Wilcoxon signed rank test. Categorical data were analyzed using Chi-square test. RESULTS: In total, 72 participants of the add-on homeopathy (AoH) group showed conversion of RT-PCR status to negative, in an average time of 7.53 ± 4.76 days (mean ± SD), as compared with 11.65 ± 9.54 days in the add-on placebo (AoP) group (p = 0.001). The mean COOS score decreased from 4.26 ± 0.44 to 3.64 ± 1.50 and from 4.3 ± 0.46 to 4.07 ± 1.8 in the AoH and AoP groups respectively (p = 0.130). The mortality rate for the AoH group was 9.7% compared with 17.3% in the AoP group. The MYMOP2 scores between the two groups differed significantly (p = 0.001), in favor of AoH. Inter-group differences in the pre- and post- mean values of C-reactive protein, fibrinogen, total leukocyte count, platelet count and alkaline phosphatase were each found to be statistically significant (p <0.05), favoring AoH; six other biochemical parameters showed no statistically significant differences. CONCLUSION: The study suggests homeopathy may be an effective adjunct to standard care for treating moderate and severe COVID-19 patients. More rigorous, including double-blinded, studies should be performed to confirm or refute these initial findings.

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats.

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Homoeopathic Medicine Arsenicum album 30 C for Covid-19 in 2020: A Retrospective Analysis from Mass-level Data.

Background and Objective: Homoeopathy has played a notable role in managing epidemics in the past. The Ministry of Ayush, Government of India, declared Arsenicum album 30 C as a prophylactic for Covid-19, which was followed by the distribution of the medicine across India. The Central Council for Research in Homoeopathy (CCRH) collected post-prophylactic consumption data of individuals from various colleges over months, which created a data pool. Considering the importance of these mass-level data and their possible impact on public healthcare decisions, the information gathered from this heterogeneous population cohort was subjected to a retrospective data analysis to observe the incidence of Covid-19 in the community. Methods: Data from 50 colleges from February-August 2020 showed that 10.6 million people in 13 states of India received prophylactic medicine during the study period. The data was collected from individuals three weeks following prophylactic consumption for a retrospective analysis. The incidence of Covid-19 was assessed. Results: The data of 584 980 individuals who met the study criteria were included in the analysis. The incidence of Covid-19 in the population cohort was 13.58 per 10 000-person weeks (95% CI, 13.04 to 14.14), which remained near-constant over time despite the increasing disease burden in the country (12.87 to 14.52 per 10 000-person weeks). Consumption of the prophylactic significantly reduced the risk of contracting Covid-19 in high-risk groups as compared to their counterparts. Conclusion: The study concludes that Arsenicum album 30 C has a potential prophylactic effect against Covid-19. Further controlled studies are recommended to establish a causal relation.

Comparative Effectiveness of Pre-Identified Homeopathic Medicines in Asymptomatic COVID-19 Individuals Receiving Standard Care-An Open-Label, Randomized, Controlled Exploratory Trial.

BACKGROUND: Asymptomatic COVID-19 subjects can transmit the infection for as many as 14 days and are regarded as a significant factor in the rapid spread of the COVID-19 pandemic. This exploratory study aimed to determine any additional benefits of selected homeopathic medicines compared with placebo in asymptomatic COVID-19 individuals receiving standard care. METHODS: This open-label, randomized, placebo-controlled, exploratory trial was undertaken at a COVID Care Centre (CCC) in Madhya Pradesh, India. Patients (n = 200, 18-65 years, both sexes) having a positive RT-PCR and asymptomatic during admission were enrolled. They were randomly assigned to one of four groups (each n = 50): Arsenicum album 30C (Ars. alb.), Camphora 1M (Camph.), Bryonia alba 30C (Bry. alb.) and placebo (Pl.). All the patients were given standard care. The primary outcome was the number of patients becoming RT-PCR negative for SARS-CoV-2 at days 5, 10 and 15. RESULTS: In total, 200 asymptomatic COVID-19 patients were enrolled. One hundred and seventy-seven patients became RT-PCR negative by day 15; 88%, 80%, 98% and 88% from Ars. alb., Camph., Bry. alb. and Pl. respectively. A Chi-square test of association for the total patients who became RT-PCR negative for SARS-Cov-2 in each group showed a marginal statistical significance (Chi-square: 8.1, p = 0.04). A two-proportion Z-test comparing each pre-identified homeopathic medicine with placebo showed marginal statistical significance (p = 0.05) for Bry alb. only. Median time in days to RT-PCR negative (Kaplan Meier analysis) was 10 days in each of the groups. CONCLUSION: There was some evidence that, compared with Ars alb., Camph. or Pl., Bry. alb. was associated with an increased number of patients who became RT-PCR negative for COVID-19 by day 15. The possible effect exerted needs to be investigated in additional research.

Effectiveness of Arsenicum album 30C in Prevention of COVID-19 in Individuals Residing in Containment Zones of Delhi-A Prospective, Community-based, Parallel Cohort Study.

OBJECTIVE: This work was undertaken to evaluate the protective effect of Arsenicum album 30C against COVID-19. DESIGN: The work was designed as a prospective parallel cluster cohort study. INTERVENTION: Participants were enrolled in a homeopathy intervention (HI) cohort (who received Arsenicum album) or in a non-intervention (NI) cohort (who received no systematic intervention) from COVID-19 containment areas of Delhi. Individuals of age 5 years or above were given four medicated pills of Arsenicum album 30C, while those from 1 to 5 years old were given two medicated pills in each dose. RESULTS: The analysis included 10,180 individuals residing in 11 COVID-19 containment areas in Delhi, out of which 6,590 individuals were in the HI cohort and 3,590 individuals were in the NI cohort. The overall protective effect of Arsenicum album 30C was 83.43% (95% confidence interval [CI], 76.77 to 88.17): 45 cases per 6,590 (8.34 per 10,000 person-weeks) in the Arsenicum album 30C group versus 143 cases per 3,590 (45.01 per 10,000 person-weeks) in the NI cohort. The protective effect of Arsenicum album 30C against laboratory confirmed COVID-19 was 74.40% (95% CI, 55.08 to 85.41): 18 cases per 6,590 (3.32 per 10,000 person-weeks) in the Arsenicum album 30C group versus 38 cases per 3,590 (11.85 per 10,000 person-weeks) in the NI cohort. CONCLUSION: The use of Arsenicum album 30C was associated with some protection against probable and laboratory-confirmed COVID-19 in a containment-zone setting. Randomized controlled trials are needed to confirm or refute these results.

Preparation, Standardization and Anti-plasmodial Efficacy of Novel Malaria Nosodes.

BACKGROUND: Resistance to artemisinin and its partner drugs has threatened the sustainability of continuing the global efforts to curb malaria, which urges the need to look for newer therapies to control the disease without any adverse side effects. In the present study, novel homeopathic nosodes were prepared from Plasmodium falciparum and also assessed for their in vitro and in vivo anti-plasmodial activity. METHODS: Three nosodes were prepared from P. falciparum (chloroquine [CQ]-sensitive [3D7] and CQ-resistant [RKL-9] strains) as per the Homeopathic Pharmacopoeia of India, viz. cell-free parasite nosode, infected RBCs nosode, mixture nosode. In vitro anti-malarial activity was assessed by schizont maturation inhibition assay. The in vitro cytotoxicity was evaluated by MTT assay. Knight and Peter's method was used to determine in vivo suppressive activity. Mice were inoculated with P. berghei-infected erythrocytes on day 1 and treatment was initiated on the same day. Biochemical, cytokine and histopathological analyses were carried out using standard methods. RESULTS: In vitro: the nosodes exhibited considerable activity against P. falciparum with maximum 71.42% (3D7) and 68.57% (RKL-9) inhibition by mixture nosode followed by cell-free parasite nosode (62.85% 3D7 and 60% RKL-9) and infected RBCs nosode (60.61% 3D7 and 57.14% RKL-9). The nosodes were non-toxic to RAW macrophage cell line with >70% cell viability. In vivo: Considerable suppressive efficacy was observed in mixture nosode-treated mice, with 0.005 ± 0.001% parasitemia on day 35. Levels of liver and kidney function biomarkers were within the normal range in the mixture nosode-treated groups. Cytokine analysis revealed increased levels of IL-4 and IL-10, whilst a decline in IL-17 and IFN-γ was evident in the mixture nosode-treated mice. CONCLUSION: The mixture nosode exhibited promising anti-malarial activity against P. falciparum and P. berghei. Biochemical and histopathological studies also highlighted the safety of the nosode for the rodent host. The study provides valuable insight into a novel medicament that has potential for use in the treatment of malaria.

Efficacy of Chininum Sulphuricum 30C against Malaria: An in vitro and in vivo Study.

BACKGROUND: New effective, economical and safe antimalarial drugs are urgently needed due to the development of multi-drug-resistant strains of the parasite. Homeopathy uses ultra-diluted doses of various substances to stimulate autoregulatory and self-healing processes to cure various ailments. The aim of the study was to evaluate the in vitro and in vivo antimalarial efficacy of a homeopathic drug, Chininum sulphuricum 30C. METHODS: In vitro antiplasmodial activity was screened against the P. falciparum chloroquine-sensitive (3D7) strain, and cell viability was assessed against normal human dermal fibroblasts and HepG2 cells. Suppressive, preventive and curative studies were carried out against P. berghei-infected mice in vivo. RESULTS: Chininum sulphuricum (30C) revealed good antiplasmodial activity in vitro, with 92.79 ± 6.93% inhibition against the 3D7 strain. The cell viability was 83.6 ± 0.6% against normal human dermal fibroblasts and 95.22 ± 5.1% against HepG2 cells. It also exhibited suppressive efficacy with 95.56% chemosuppression on day 7 with no mortality throughout the follow-up period of 28 days. It also showed preventive activity against the disease. Drug treatment was also safe to the liver and kidney function of the host as evidenced by biochemical studies. CONCLUSION: Chininum sulphuricum 30C exhibited considerable antimalarial activity along with safety to the liver and kidney function of the host.

Evidence for Reversal of Immunosuppression by Homeopathic Medicine to a Predominant Th1-type Immune Response in BALB/c Mice Infected with Leishmania donovani.

BACKGROUND: Visceral leishmaniasis (VL) is a neglected tropical disease that is fatal if treatment is not given. The available chemotherapeutic options are unsatisfactory, and so complementary therapies like homeopathy might be a promising approach. METHODS: A nosode from a pure axenic culture of Leishmania donovani was prepared and screened for its anti-leishmanial potential both in an in-vitro and an in-vivo experimental approach. RESULTS: Leishmania donovani amastigote promastigote nosode (LdAPN 30C) exhibited significant anti-leishmanial activity against the promastigote forms of Leishmania donovani and was found to be safe. A study conducted on VL-infected mice revealed that LdAPN 30C resolved the disease by modulating the host immune response toward the Th1 type through upregulating the pro-inflammatory cytokines (IFN-γ and IL-17) and inducing nitric oxide (NO) levels in the infected macrophages. The hepatic parasite load was also found to be significantly decreased. The nosode was found to be safe, as no histological alterations in the liver or kidney were observed in the animals treated with the LdAPN 30C. CONCLUSION: This is the first study in which an axenic culture of Leishmania donovani has been used for the preparation of a homeopathic medication. The study highlights the anti-leishmanial and immunomodulatory potential of a homeopathic nosode in experimental VL.

Targeting Aberrant Expression of STAT3 and AP-1 Oncogenic Transcription Factors and HPV Oncoproteins in Cervical Cancer by Berberis aquifolium.

Background: Present study examines phytochemical preparation that uses berberine's plant source B. aquifolium root for availability of similar anti-cervical cancer (CaCx) and anti-HPV activities to facilitate repurposing of the B. aquifolium based drug in the treatment of CaCx. Purpose: To evaluate therapeutic potential of different concentrations of ethanolic extract of B. aquifolium root mother tincture (BAMT) against HPV-positive (HPV16: SiHa, HPV18: HeLa) and HPV-negative (C33a) CaCx cell lines at molecular oncogenic level. Materials and Methods: BAMT was screened for anti-proliferative activity by MTT assay. Cell cycle progression was analyzed by flowcytometry. Then, the expression level of STAT3, AP-1, HPV E6 and E7 was detected by immunoblotting, whereas nuclear localization was observed by fluorescence microscopy. Phytochemicals reportedly available in BAMT were examined for their inhibitory action on HPV16 E6 by in silico molecular docking. Results: BAMT induced a dose-dependent decline in CaCx cell viability in all cell types tested. Flowcytometric evaluation of BAMT-treated cells showed a small but specific cell growth arrest in G1-phase. BAMT-treatment resulted in reduced protein expression of key transcription factors, STAT3 with a decline of its active form pSTAT3 (Y705); and components of AP-1 complex, JunB and c-Jun. Immunocytochemistry revealed that BAMT did not prevent the entry of remnant active transcription factor to the nucleus, but loss of overall transcription factor activity resulted in reduced availability of transcription factors in the cancer cells. These changes were accompanied by gradual loss of HPV E6 and E7 protein in BAMT-treated HPV-positive cells. Molecular docking of reported active phytochemicals in B. aquifolium root was performed, which indicated a potential interference of HPV16 E6's interaction with pivotal cellular targets p53, E6AP or both by constituent phytochemicals. Among these, berberine, palmatine and magnoflorine showed highest E6 inhibitory potential. Conclusion: Overall, BAMT showed multi-pronged therapeutic potential against HPV infection and cervical cancer and the study described the underlying molecular mechanism of its action.

Stem cell therapy: A paradigm shift in breast cancer treatment.

As per the latest Globocan statistics, the high prevalence rate of breast cancer in low- and middle-income countries has led to it becoming the most common cancer to be diagnosed, hence posing a major public health challenge. As per this data, more than 11.7% of the estimated new cancer cases in 2020 were due to breast cancer. A small but significant subpopulation of cells with self- renewing ability are present in the tumor stroma and have been given the nomenclature of cancer stem cells (CSCs). These cells display a high degree of plasticity owing to their ability to transition from the slowly cycling quiescent phase to the actively proliferating phenotype. This attribute of CSCs allows them to differentiate into various cell types having diverse functions. Breast CSCs have a pivotal role in development, metastasis, treatment resistance and relapse of breast cancers. This review focuses on the pathways regulating breast CSC maintenance and the current strategies that are being explored for directing the development of novel, targeted, therapeutic approaches for limiting and eradicating this aberrant stem cell population.

Clinical Repurposing of Medicines is Intrinsic to Homeopathy: Research Initiatives on COVID-19 in India.

As at mid-October 2020, the coronavirus disease 2019 (COVID-19) pandemic has been continuing on the rise across the globe, including in India. Historically, homeopathy has been used in a number of epidemics/pandemics. The development of homeopathic medicines is approached uniquely through "drug provings" and clinical verification; these two intrinsic processes establish the background for the application of homeopathic medicines, regardless of nosological diagnosis. This article reflects research initiatives on COVID-19 in India and identifies studies listed in the Clinical Trial Registry-India database. We identified 29 studies being undertaken in different settings, including those in conventional medicine: 20 randomized controlled trials (RCTs) and 9 observational studies. Fifteen studies are aimed at prophylaxis and 14 are aimed at treatment. Amongst the treatment studies, 11 are focused on efficacy or comparative effectiveness. The findings might provide evidence for clinically repurposing some of homeopathy's medicines, an approach that is intrinsic to the therapy, enabling their use in COVID-19 as an adjuvant or stand-alone to help reduce costs and improve patient recovery.

Wound Healing Activity of a Novel Formulation SKRIN via Induction of Cell Cycle Progression and Inhibition of PCNA-p21 Complex Interaction Leading to Cell Survival and Proliferation.

The process of wound healing is a dynamic event that starts with inflammation, proliferation, and cell migration of various types of fibroblast cells. Therefore, identification of potential molecules which may increase the wound healing capacity of fibroblast cells is crucial. A novel hydroalcoholic formulation of belladonna (SKRIN), was developed and characterized by GC-MS/MS, DLS, TEM, and AFM and was found to contain atropine and scopolamine exhibit in aggregated nanosized particles. SKRIN-mediated fibroblast cell survival was elucidated in the presence of H2O2 by MTT and flow cytometry based assays. With an EC50 of 4.41 µg/mL, SKRIN treatment showed significant increase in cell survival that was evident from a 1.11-fold increase (p < 0.0122) in the live cell population and 4.21-fold (p < 0.0001) and 2.59-fold (p < 0.0001) reductions in the early and late apoptotic cell populations, respectively. SKRIN-mediated wound healing was measured by cell scratch assay and cell cycle analysis. During the wound closure phenomenon, SKRIN increases repairing fibroblast cell proliferation by 1.24-fold (p = 0.0481) and increases the count of G2/M phase cells by 1.76-fold (p = 0.0002) which was confirmed by increased PCNA and reduced p21 protein expressions probably mediated by molecular interactions of PCNA-p21 complex with alkaloids present in SKRIN. Relative gene expression analysis further showed that SKRIN increases the PI3K, Akt, and NF-κB expression. Our data suggests that SKRIN exhibits wound healing property by increasing cell survival and repairing fibroblast proliferation via activation of the PI3K-Akt-NF-κB pathway probably mediated by inhibition of PCNA-p21 complex interaction.