Role of auto-antibodies in the mechanisms of dengue pathogenesis and its progression: a comprehensive review.

A complex interaction among virulence factors, host-genes and host immune system is considered to be responsible for dengue virus (DENV) infection and disease progression. Generation of auto-antibodies during DENV infection is a major phenomenon that plays a role in the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. Hemostasis, thrombocytopenia, hepatic endothelial dysfunction, and autoimmune blistering skin disease (pemphigus) are different clinical manifestations of dengue pathogenesis; produced due to the molecular mimicry of DENV proteins with self-antigens like coagulation factors, platelets and endothelial cell proteins. This review elaborately describes the current advancements in auto-antibody-mediated immunopathogenesis which inhibits coagulation cascade and promotes hyperfibrinolysis. Auto-antibodies like anti-endothelial cell antibodies-mediated hepatic inflammation during severe DENV infection have also been discussed. Overall, this comprehensive review provides insight to target auto-antibodies that may act as potential biomarkers for disease severity, and a ground for the development of therapeutic strategy against DENV.

Homoeopathy vs. conventional primary care in children during the first 24 months of life-a pragmatic randomised controlled trial.

To compare the difference between primary homoeopathic and conventional paediatric care in treating acute illnesses in children in their first 24 months of life. One hundred eight Indian singleton newborns delivered at 37 to 42 weeks gestation were randomised at birth (1:1) to receive either homoeopathic or conventional primary care for any acute illness over the study period. In the homoeopathic group, conventional medical treatment was added when medically indicated. Clinicians and parents were unblinded. Children in the homoeopathic group experienced significantly fewer sick days than those in the conventional group (RR: 0.37, 95% CI: 0.24-0.58; p < 0.001), with correspondingly fewer sickness episodes (RR: 0.53, 95% CI: 0.32-0.87; p = .013), as well as fewer respiratory illnesses over the 24-month period. They were taller (F (1, 97) = 8.92, p = .004, partial eta squared = 0.84) but not heavier than their conventionally treated counterparts. They required fewer antibiotics, and their treatment cost was lower. CONCLUSION: Homoeopathy, using conventional medicine as a safety backdrop, was more effective than conventional treatment in preventing sick days, sickness episodes, and respiratory illnesses in the first 24 months of life. It necessitated fewer antibiotics and its overall cost was lower. This study supports homoeopathy, using conventional medicine as a safety backdrop, as a safe and cost-effective primary care modality during the first 2 years of life. TRIAL REGISTRATION: Clinical Trial Registry-India (2018/09/015641). https://ctri.nic.in/Clinicaltrials/login.php What is Known: • Due to their holistic nature, many Complementary and Alternative Medical (CAM) modalities are not readily amenable to assessment by head-to-head RCT for a given Indication. • We propose a pragmatic, RCT comparing homoeopathic with conventional medicine as a system. WHAT IS NEW: • Homoeopathic was apparently superior to conventional primary care in preventing sick days, sickness episodes, and respiratory illness episodes and was significantly associated with growth in height but not weight and required fewer antibiotics in children from birth to 24 months of age.

Effectiveness of Eupatorium Perfoliatum 30C in Preventing Dengue Fever-A Prospective, Community-Based, Open Label, Parallel Cohort Study in Delhi, India.

OBJECTIVE: The study was undertaken to evaluate the protective effect of Eupatorium perfoliatum (EP) 30C on the incidence of dengue fever. DESIGN: This study was designed as a prospective, open label, parallel cohort study. INTERVENTIONS: Participants were enrolled in two medicine cohort (MC) communities and one control cohort (CC) community. Participants in MC who were more than 5 years of age received four medicated globules and those aged between 1 and 5 years received two medicated globules of EP 30C once a week for 10 weeks. Participants in CC received no medical intervention. Both cohorts received information and educational material regarding dengue. OUTCOME MEASURES: The primary outcome was incidence of dengue cases based on laboratory confirmation or the clinical definition of dengue as per the case definition notified by the National Vector-Borne Disease Control Program, Government of India, during the 14 weeks of intervention and observation. RESULTS: The analysis included 20,607 participants residing in three slums of Delhi, of which MC and CC included 15,298 and 5,309 participants respectively. The overall protective effect of EP 30C in MC against probable/laboratory-confirmed dengue was 59.59% (95% confidence interval [CI], 50.74 to 66.85, p = 0.0001). The overall protective effect of EP 30C against laboratory-confirmed dengue was 72.78% (95% CI, 54.45 to 83.74, p = 0.0001): 26 cases per 15,298 (0.13 per 1,000 person-weeks) in MC versus 33 cases per 5,309 (0.46 per 1,000 person-weeks) in CC. CONCLUSION: The use of EP 30C was associated with some protection against probable and laboratory-confirmed dengue.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

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.

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.

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.

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.

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.

The Effect of Iodium 30c on Experimental Visceral Leishmaniasis.

BACKGROUND: Leishmaniasis is one of several neglected tropical diseases that warrant serious attention. A disease of socio-economically poor people, it demands safer and cheaper drugs that help to overcome the limitations faced by the existing anti-leishmanials. Complementary or traditional medicines might be a good option, with an added advantage that resistance may not develop against these drugs. Thus, the present investigation was performed to evaluate the anti-leishmanial efficacy of an ultra-diluted homeopathic medicine (Iodium 30c) in experimental visceral leishmaniasis (VL). METHODS: Compliant with strict ethical standards in animal experimentation, the study was performed in-vivo in inbred BALB/c mice which were injected intravenously with 1 × 107 promastigotes of Leishmania donovani before (therapeutic) or after (prophylactic) treatment with Iodium 30c for 30 days. In other groups of mice (n = 6 per group), amphotericin B served as positive control, infected animals as the disease control, while the naïve controls included normal animals; animals receiving only Iodium 30c or Alcohol 30c served as sham controls. The anti-leishmanial efficacy was assessed by determining the hepatic parasite load and analysing percentages of CD4+ and CD8+ T cells. Biochemical analysis and histological studies were performed to check any toxicities. RESULTS: Iodium-treated animals showed a significantly reduced parasite load (to 1503 ± 39 Leishman Donovan Units, LDU) as compared with the infected controls (4489 ± 256 LDU) (p < 0.05): thus, the mean therapeutic efficacy of Iodium 30c was 66.5%. In addition, the population of CD4+ and CD8+ T cells was significantly increased (p < 0.05) after treatment. No toxicity was observed, as evidenced from biochemical and histopathological studies of the liver and kidneys. Efficacy of Iodium 30c prophylaxis was 58.3%, while the therapeutic efficacy of amphotericin B was 85.9%. CONCLUSION: This original study has shown that Iodium 30c had significant impact in controlling parasite replication in experimental VL, though the effect was less than that using standard pharmaceutical treatment.

In Vitro Assessment of Homeopathic Potencies of Hydrastis canadensis on Hormone-Dependent and Independent Breast Cancer.

BACKGROUND: Breast cancer is the second leading cause of cancer-related deaths in women. Conventional treatment such as chemotherapy, hormonal therapy and radiotherapy has decreased the mortality rate among cancer patients but has also revealed long-term side effects. Drug resistance and toxicity to normal cells compound the problems associated with the use of modern medicines. Hence, complementary or alternative treatment options are being explored. The current study, using different homeopathic potencies of Hydrastis canadensis, was conducted to distinguish between any effects they might have on hormone-dependent and independent breast cancer. MATERIALS AND METHODS: The cytotoxic effect of homeopathic medicine Hydrastis on hormone-dependent (MCF 7) and hormone-independent (MDA-MB-468) breast cancer cells was assessed using viability and colony-forming assays after 48 or 72 hours of treatment. Flow cytometry-based Annexin V-PI (propidium iodide), caspase 3 and cell cycle analysis was performed following treatment of cells with mother tincture or various potencies of Hydrastis (1C, 2C, 30C, 200C). RESULTS: Different potencies of Hydrastis displayed selective cytotoxic effects against MCF 7 cells, but only marginal effects against MDA-MB-468. The maximum cytotoxicity was established in the case of 1C following 72 hours of treatment. Treatment of breast cancer cells revealed an increase in the G0/G1 cell population, along with an increase in the caspase 3 levels and induction of apoptosis. CONCLUSION: Hydrastis may have a selective cytotoxic effect against hormone-dependent breast cancer MCF 7 cells, leading to cell cycle arrest in the G0/G1 phase, which could be the plausible reason for the induction of apoptosis. The results need to be validated in vivo.

Effect of Adjuvant Homeopathy with Usual Care in Management of Thrombocytopenia Due to Dengue: A Comparative Cohort Study.

BACKGROUND: Dengue is an emerging threat to public health. At present, no clear modalities are available for the prevention and management of thrombocytopenia due to dengue. This article reports the clinical outcomes of integrative homeopathic care in a hospital setting during a severe outbreak of dengue in New Delhi, India, during the period September to December 2015. METHODS: Based on preference, 138 patients received a homeopathic medicine along with usual care (H+UC), and 145 patients received usual care (UC) alone. Assessment of thrombocytopenia (platelet count < 100,000/mm3) was the main outcome measure. Kaplan-Meier analysis enabled comparison of the time taken to reach a platelet count of 100,000/mm3. RESULTS: There was a statistically significantly greater rise in platelet count on day 1 of follow-up in the H+UC group compared with UC alone (mean difference = 12,337; 95% confidence interval [CI], 5,421 to 19,252; p = 0.001). This trend persisted until day 5 (mean difference = 14,809; 95% CI, 1,615 to 28,004; p = 0.02). The time taken to reach a platelet count of 100,000/mm3 was nearly 2 days earlier in the H+UC group compared with UC alone (H+UC: 3.44 days ± standard error of the mean [SEM] 0.18; 95% CI, 3.08 to 3.80; UC: 5.28 days ± SEM 0.29; 95% CI, 4.71 to 5.86; p < 0.001). CONCLUSION: These results suggest a positive role of adjuvant homeopathy in thrombocytopenia due to dengue. Randomized controlled trials may be conducted to obtain more insight into the comparative effectiveness of this integrative approach.

Effect of Homeopathic Dilutions of Cuprum Arsenicosum on the Electrical Properties of Poly(Vinylidene Fluoride-Co-Hexafluoropropylene).

BACKGROUND: We report the effects of nanoparticles in homeopathic preparations of copper salts on the electrical properties of polymer film. Previous work showed that the incorporation of metal-derived homeopathic medicines increases the dielectric constant and alternating current (AC) conductivity of an electroactive polymer film that is commonly used as a capacitor in the electronic industry.We report here the effect of dilution of one homeopathic medicine, Cuprum arsenicosum (CuAs), at 200C potency on the electrical properties of the polymer film of poly(vinylidene fluoride-co-hexafluoropropylene). METHODS: CuAs 200c was incorporated in the film by the solution casting method. The electrical characteristics were measured at different frequencies using an inductance, capacitance, and resistance meter. Fourier transform infrared spectroscopy (FTIR) was performed to detect phase change in the polymer film due to the incorporation of CuAs. Morphology and particle size were studied using field emission scanning electron microscopy (FESEM) and energy dispersive X-ray (EDX) spectroscopy. RESULTS: At 10 kHz frequency, both dielectric constant and AC conductivity increased approximately 18 times for the polymer film when incorporated with 2 mL CuAs at 200C potency. FTIR indicated the increase in conducting phase, while FESEM and EDX confirmed the presence of spherical CuAs particles. CONCLUSION: The incorporation of CuAs in the electroactive polymer film enhances the conductivity and dielectric constant. We conclude that these changes arise from the change in phase of the polymer film, and because of the presence of two different metals that affects the interfacial polarization.

Homeopathic preparation of Allium sativum abrogates OxLDL mediated atherogenic events in macrophages: An invitro and in silico approach.

BACKGROUND: Oxidized LDL (OxLDL), the key player in atherogenesis modulates endothelial dysfunction, initiates monocyte recruitment, accentuates foam cell formation, and flares up inflammatory and apoptotic events. Even though homeopathic preparation of Allium sativum has been proved to be an anti-inflammatory, anti-apoptotic and anti-atherogenic agent, its mechanism of action on abrogating OxLDL mediated foam cell formation is yet to be explored. OBJECTIVE: This study was designed to bring out the role of homeopathic preparation of Allium sativum in curbing OxLDL mediated cellular inflammation in IC-21 cells exposed with OxLDL. MATERIALS AND METHODS: OxLDL was used to induce oxidative damage in the IC-21 macrophage cells. Assessment of inflammatory cytokines, localization of NFκB, detection of apoptosis and the in silico analysis were performed in this study. RESULTS: The current study portrays the efficacy of homeopathy medicine as an anti-inflammatory agent, in reducing the levels of inflammatory cytokines and its mRNA expression, suppressing the activity of NFκB and preventing apoptosis in OxLDL treated IC-21 cells. CONCLUSION: To conclude, homeopathic preparation of Allium sativum 6C and 30C potencies are capable of controlling the transcriptional activity of NFκB and apoptosis in IC-21 cells exposed to OxLDL. These results implicate that Allium sativum homeopathic drug can be used as anti-inflammatory agent in reducing atherogenic events as it is capable of preventing OxLDL-mediated injury to macrophages.

Epidemiology and impact of chronic disease multimorbidity in India: a systematic review and meta-analysis.

Objectives: This is the first systematic review and meta-analysis of the prevalence of multimorbidity, its risk factors including socioeconomic factors, and the consequences of multimorbidity on health systems and broader society in India. Methods: A systematic review of both published and grey literature from five databases (Medline, Embase, EBSCO, Scopus, and ProQuest) was conducted including original studies documenting prevalence or patient outcomes associated with multimorbidity among adults in India. We excluded studies that did not explicitly mention multimorbidity. Three independent reviewers did primary screening based on titles and abstracts followed by full-text review for potential eligibility. The risk of bias was independently assessed by two reviewers following the Appraisal Tool for Cross-Sectional Studies. We presented both qualitative and quantitative (through meta-analysis) summaries of the evidence. The protocol for this study was prospectively registered with PROSPERO (CRD42021257281). Results: The review identified 5442 articles out of which 35 articles were finally included in this study. Twenty-three studies were based on the primary data while 12 used secondary data. Eleven studies were conducted in hospital/primary care setting while 24 were community-based. The pooled prevalence of multimorbidity based on (n=19) studies included for meta-analysis was 20% (95% CI: 19% to 20%). The most frequent outcomes were increased healthcare utilization, reduced health-related quality of life, physical and mental functioning. Conclusion: We identified a wide variance in the magnitude of multimorbidity across age groups and regions with most of the studies from eastern India. Nation-wide studies, studies on vulnerable populations and interventions are warranted.

Arsenic album 30C exhibits crystalline nano structure of arsenic trioxide and modulates innate immune markers in murine macrophage cell lines.

Macrophages are associated with innate immune response and M1-polarized macrophages exhibit pro-inflammatory functions. Nanoparticles of natural or synthetic compounds are potential triggers of innate immunity. As2O3 is the major component of the homeopathic drug, Arsenic album 30C.This has been claimed to have immune-boosting activities, however, has not been validated experimentally. Here we elucidated the underlying mechanism of Ars. alb 30C-mediated immune priming in murine macrophage cell line. Transmission Electron Microscopy (TEM) and X-ray diffraction (XRD) used for the structural analysis of the drug reveals the presence of crystalline As2O3 nanoparticles of cubic structure. Similarly, signatures of M1-macrophage polarization were observed by surface enhanced Raman scattering (SERS) in RAW 264.7 cells with concomitant over expression of M1 cell surface marker, CD80 and transcription factor, NF-κB, respectively. We also observed a significant increase in pro-inflammatory cytokines like iNOS, TNF-α, IL-6, and COX-2 expression with unaltered ROS and apoptosis in drug-treated cells. Enhanced expression of Toll-like receptors 3 and 7 were observed both in transcriptional and translational levels after the drug treatment. In sum, our findings for the first time indicated the presence of crystalline As2O3 cubic nanostructure in Ars. alb 30C which facilitates modulation of innate immunity by activating macrophage polarization.

Preliminary investigation on ultra high diluted B. vulgaris in experimental urolithiasis.

PURPOSE: The study focuses on the anti-urolithiasis potential of ultra-diluted homeopathic potency of Berberis vulgaris (B. vulgaris) root bark, commonly used in homeopathic system to treat renal calculi. METHODOLOGY: B. vulgaris root bark (200c, 20 µl/100 g body weight/day, p.o, for 28 days) was tested in an animal model of urolithiasis. Urolithiasis was induced in male Wistar rats by adding 0.75% ethylene glycol (EG) to drinking water. Urine and serum samples were analyzed for calcium, magnesium, phosphorus, uric acid and creatinine. Enzymic makers of renal damage (alkaline phosphatase, lactate dehydrogenase, leucine aminopeptidase and γ-glutamyl transpeptidase) were assessed in kidney and urine. Renal tissues were analyzed for oxalate content. RESULTS: Administration of EG to rats increased the levels of the stone-forming constituents calcium, phosphorus and uric acid, in urine. Levels were normalized by B. vulgaris treatment. The decrease in the urolithiasis inhibitor magnesium in urine was prevented by treatment with B. vulgaris. Serum creatinine levels were largely normalized by B. vulgaris treatment. Hyperoxaluria induced renal damage was evident from the decreased activities of tissue marker enzymes and an apparent escalation in their activity in the urine in control animals; this was prevented by B. vulgaris treatment. CONCLUSION: Homeopathic B. vulgaris root bark has strong anti-urolithiasis potential at ultra-diluted dose.

Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic rats.

BACKGROUND: Homeopathy is a holistic method of treatment that uses microdoses of natural substances originating from plants, minerals, or animal parts. Syzygium jambolanum and Cephalandra indica are used in homeopathy for treatment of type-2 diabetes. However, the molecular mechanisms responsible for such effects are not known. METHODS: Homeopathic preparations of S. jambolanum and C. indica in mother tincture, 6c and 30c were used to examine the molecular mechanism of antidiabetic effects in the skeletal muscle of rats with high fat and fructose-induced type-2 diabetes mellitus. After 30 days treatment, fasting blood glucose, serum insulin and insulin signaling molecules in the skeletal muscle (gastrocnemius) were measured. RESULTS: Diabetic rats showed a significant decrease in serum insulin and lipid profile as well as low levels of insulin receptor (IR), v-akt murine thymoma viral oncogene homolog (Akt), p-Akt(ser473) and glucose transporter-4 (GLUT4) protein expression (p < 0.05) with a significant increase in fasting blood glucose level (p < 0.05) compared to the control group. Treatment with homeopathic remedies significantly increased the serum insulin and expression of these proteins (p < 0.05) with a significant decrease in fasting blood glucose (p < 0.05) compared to diabetic rats. CONCLUSIONS: In the present study homeopathic preparations of S. jambolanum and C. indica, including ultramolecular dilutions exhibit antidiabetic effects, improving insulin action through activation of insulin signaling molecules in skeletal muscle of type-2 diabetic rats.

Ultradiluted SARS-CoV-2 Spike Protein mitigates hyperinflammation in lung via ferritin and MMP-9 regulation in BALB/c mice.

AIM: This study investigated the prophylactic and therapeutic role of ultradiluted preparation of the Delta variant of SARS-CoV-2 recombinant spike (S) protein during S antigen-induced inflammatory process of disease progression along with the probable mechanism of action. MAIN METHODS: Ultradiluted S protein (UDSP) was prepared and administered orally to adult BALB/c mice before and after administration of S antigen intranasally. After an observation period of 72 h, animals were sacrificed and expression level of ferritin was assayed through ELISA. The genetic expressions of cytokines, IL-6, IL-10, IL-1ß, TNFα, IL-17, MMP-9, TIMP-1, ferritin light and heavy chains, and mitochondrial ferritin from lung tissues were investigated through RT-PCR. Formalin-fixed lung tissue sections were stained with hematoxylin and eosin to observe the degree of pathological changes. The activity of MMP-9 in lung tissues was investigated through gelatin zymography and immunofluorescence of MMP-9 in lung tissue sections was performed to revalidate the finding from gelatin zymography. Systems biology approach was used to elucidate a probable pathway where UDSP attenuated the inflammation through the regulation of pro- and anti-inflammatory cytokines. KEY FINDINGS: UDSP attenuated the S antigen-induced hyperinflammation in the lung by regulating pro- and anti-inflammatory cytokines, calming cytokine storm, reducing ferritin level both in transcriptional and translational levels, and restoring critical ratio of MMP-9: TIMP-1. SIGNIFICANCE: Our findings suggest a probable pathway by which UDSP might have attenuated inflammation through the regulation of cytokines, receptors, and other molecules. This proclaims UDSP as a promising antiviral agent in the treatment of COVID-19-induced immunopathogenesis.