Homeopathic Medicines Used as Prophylaxis in Kolkata during the COVID-19 Pandemic: A Community-Based, Cluster-Randomized Trial.

INTRODUCTION: There is some evidence that homeopathic treatment has been used successfully in previous epidemics, and currently some countries are testing homeoprophylaxis for the coronavirus disease 2019 (COVID-19) pandemic. There is a strong tradition of homeopathic treatment in India: therefore, we decided to compare three different homeopathic medicines against placebo in prevention of COVID-19 infections. METHODS: In this double-blind, cluster-randomized, placebo-controlled, four parallel arms, community-based, clinical trial, a 20,000-person sample of the population residing in Ward Number 57 of the Tangra area, Kolkata, was randomized in a 1:1:1:1 ratio of clusters to receive one of three homeopathic medicines (Bryonia alba 30cH, Gelsemium sempervirens 30cH, Phosphorus 30cH) or identical-looking placebo, for 3 (children) or 6 (adults) days. All the participants, who were aged 5 to 75 years, received ascorbic acid (vitamin C) tablets of 500 mg, once per day for 6 days. In addition, instructions on healthy diet and general hygienic measures, including hand washing, social distancing and proper use of mask and gloves, were given to all the participants. RESULTS: No new confirmed COVID-19 cases were diagnosed in the target population during the follow-up timeframe of 1 month-December 20, 2020 to January 19, 2021-thus making the trial inconclusive. The Phosphorus group had the least exposure to COVID-19 compared with the other groups. In comparison with placebo, the occurrence of unconfirmed COVID-19 cases was significantly less in the Phosphorus group (week 1: odds ratio [OR], 0.1; 95% confidence interval [CI], 0.06 to 0.16; week 2: OR, 0.004; 95% CI, 0.0002 to 0.06; week 3: OR, 0.007; 95% CI, 0.0004 to 0.11; week 4: OR, 0.009; 95% CI, 0.0006 to 0.14), but not in the Bryonia or Gelsemium groups. CONCLUSION: Overall, the trial was inconclusive. The possible effect exerted by Phosphorus necessitates further investigation. TRIAL REGISTRATION: CTRI/2020/11/029265.

Bryonia multiflora Extract Induces Autophagy via Regulating Long Non-coding RNAs in Breast Cancer Cells.

Bryonia multiflora, one of the species of Bryonia L. (Cucurbitaceae) genus, is a perennial, dioecious, herbaceous plant with rhizome-shaped roots. Bryonia species have anti-inflammatory, antimicrobial, cytotoxic, antioxidant, etc., activities and their components consume antitumoral effects. Purpose of the study to investigate the effect of Bryonia Multiflora extract (BMST) on breast cancer cells. Our results revealed that MCF-7 and MDA-MB-231 cells underwent significant morphological changes leading to cell rounding. No significant changes were observed in the cell viability by MTT. Acridine orange staining of our cells gave rise to think that BMST might lead our cells to autophagy. Therefore, possible molecular mechanisms underlying morphological changes such as autophagy (LC-3B, Beclin, AMBRA1) and apoptosis (Bcl-2) were evaluated on mRNA and protein levels. BMST treated MCF-7 and MDA-MB-231 cells had increased levels of autophagy markers whereas decreased levels of Bcl-2. p21 levels were also found to be increased in both cells. Analysis of lncRNA expressions has shown that BMST treatment led to changes in the expression levels of several lncRNAs playing roles in autophagy. The current study has shown that BMST induces autophagy in MCF-7 and MDA-MB-231 cells via regulating the lncRNAs revealing that BMST could be a promising therapeutic agent.

Clinical Characteristics and Remedy Profiles of Patients with COVID-19: A Retrospective Cohort Study.

OBJECTIVE: The aim of the study was to identify indicated homeopathic remedies based on the clinical characteristics of coronavirus disease 2019 (COVID-19) patients in India. METHODS: In this retrospective, cohort study, confirmed COVID-19 patients admitted at a COVID Health Centre in New Delhi between April 29 and June 17, 2020 were given conventional and homeopathic treatment. Patients were grouped into mild, moderate or severe categories of disease. Their symptomatologic profiles were analyzed to identify indicated homeopathic medicines. RESULTS: A total of 196 COVID-19 patients were admitted. One hundred and seventy-eight patients had mild symptoms; eighteen patients had moderate symptoms; no patients with severe symptoms were included as they were referred to tertiary care centers with ventilatory support. The mean age of patients with mild symptoms was significantly lower (38.6 years; standard deviation or SD ± 15.8) compared with patients in the moderate category (66.0 years; SD ± 9.09). The most important symptoms identified were fever (43.4%), cough (47.4%), sore throat (29.6%), headache (18.4%), myalgia (17.9%), fatigue (16.8%), chest discomfort (13.8%), chills (12.6%), shortness of breath (11.2%) and loss of taste (10.2%). Twenty-eight homeopathic medicines were prescribed, the most frequently indicated being Bryonia alba (33.3%), Arsenicum album (18.1%), Pulsatilla nigricans (13.8%), Nux vomica (8%), Rhus toxicodendron (7.2%) and Gelsemium sempervirens (5.8%), in 30C potency. CONCLUSION: Data from the current study reveal that Arsenicum album, Bryonia alba, Pulsatilla nigricans, Nux vomica, Rhus toxicodendron and Gelsemium sempervirens are the most frequently indicated homeopathic medicines. A randomized controlled clinical trial based on this finding is the next step.

Antitumor Effect of Bryonia dioïca Methanol Extract: In Vitro and In Vivo Study.

Aim: A large number of plant-derived products have been approved for the treatment of numerous types of cancer, and these products have also shown to reduce the effects of metastatic cancer. The aim of this study is to evaluate the anticancer effects of a methanolic extract of Bryonia dioïca root (M extract) against B16F10 melanoma cancer cells in vitro as well as in vivo.Results: It was shown to induce apoptosis, in vitro, and to inhibit cell growth by arresting cell cycle progression in SubG1 phase. Mice bearing the melanoma cells were used to confirm any in vivo effectiveness of the M extract as an antitumor promoting agent. In mice dosed with 50 mg M/kg/d (for 28 days), tumor weight was inhibited by 65.03% compared to that in mice that did not receive the product. Our results demonstrate on the one hand, that this inhibition was accompanied by a drastic decrease regulation of complex FAK, Src, ERK, p130Cas and paxillin. On the other hand, it was marked by a measurable decrease of the metastatic descent in the lungs.Conclusions: These effects could be ascribed to the presence of bryoniosides and cucurbitacins such as cucurbitacin A and cucurbitacin G in M extract.

Case Reports of Five Cancer Patients with Unusual Course.

INTRODUCTION: The analysis of the periodic table of elements by Jan Scholten opened the way for a new kind of classification and repertorisation of homeopathic remedies. Thereby, group analysis (resorting to series and stages) makes precise prescriptions possible. This approach appears to yield striking results, even in severe cases. Whereas Hahnemann stressed the emotional state ('Gemüthssymptome', Organon § 210) when choosing a remedy, Scholten 200 years later investigated the mental picture that represents a life conflict or even a life theme that may maintain the disease process. The person's environment, emotional traumas or a conflict drives him or her to suppress and dissect painful emotions. Such compensations can become subconscious and so strong that they can no longer be controlled; they then influence the patient with a highly destructive energy. METHODS: We present five case reports, each dealing with an unusual clinical course of severe cancer associated with homeopathic treatment using the Scholten method. RESULTS: By presenting these cases, we consider how the constitution (lifelong signs and symptoms of the patient) and the mental state are interwoven and, as a complex mechanism, might provoke disease. CONCLUSION: The appropriate homeopathic remedy, reflecting the Scholten approach, seemed to have beneficial impact on the disease process of the five individuals presented.

Probing the wound healing potential of biogenic silver nanoparticles.

OBJECTIVE: Silver nanoparticles (AgNPs) are known for their antimicrobial profile and wound healing activities. However, cytotoxicity and cosmetic abnormalities associated with silver pose a major challenge in their translation for therapeutic applications. Our objective was to develop biogenic AgNPs, using a single-step green synthesis, and to investigate their in vitro and in vivo behaviour as wound-healing agents. METHOD: AgNPs were prepared using the green synthesis approach with aqueous Bryonia laciniosa leaves extract. The AgNPs were then evaluated for physicochemical properties, stability, and antimicrobial and in vivo wound healing activities. RESULTS: Stable AgNPs with characteristic absorption at 408nm and 15±3nm particle size were generated via the active involvement of Bryonia laciniosa. No loss of stability was detected after 6 months at room temperature. Antibacterial activity was observed against both Gram-negative and Gram-positive bacteria with no cytotoxicity observed in vitro at a concentration of 200 µg/mL and effective cytokine modulation. In vivo wound healing experiments showed improved wound contracting ability in rats where, after 14 days, wound alleviation was 47.1±2.2% in the control groups, compared with 78.1±1.4% and 92.6±6.7% for a silver-based marketed cream and the AgNPs, respectively. CONCLUSION: The developed AgNPs proved to be superior wound healing agents owing to scarless healing with insignificant inflammation and toxicity. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

Carotenoid content of wild edible young shoots traditionally consumed in Spain (Asparagus acutifolius L., Humulus lupulus L., Bryonia dioica Jacq. and Tamus communis L.).

BACKGROUND: Wild vegetables have traditionally been consumed as part of the Mediterranean diet, being valuable sources of nutrients and bioactive compounds. The objective of this work was to analyse the carotenoid content of the edible young shoots of four species (Asparagus acutifolius L., Humulus lupulus L., Bryonia dioica Jacq. and Tamus communis L.) as part of a wider study on the characterisation of the nutritional composition of wild edible plants commonly consumed in Spain. Samples were gathered from two locations in Central Spain for two consecutive years. RESULTS: Lutein, ß-carotene, neoxanthin and violaxanthin were quantified by high-performance liquid chromatography with a photodiode array detector. Median concentration ranges (µg g(-1) edible wet weight) were: ß-carotene, 3.39-6.69, lutein, 5.44­19.13;neoxanthin, 5.17-17.37; and violaxanthin, 2.08-8.93. The highest carotenoid content was that of B. dioica (59.01 µg g(-1)) and the lowest was found in A. acutifolius (17.58 µg g(-1)) [corrected]. CONCLUSION: Our results show that these wild young shoots are richer sources of carotenoids than many of the commercially available leafy vegetables.

Appraising the Phytochemical and Therapeutic Perspectives of Bryonia laciniosa: A Literature Metasynthesis.

BACKGROUND: Nature has bestowed mother Earth with an array of herbals utilized as therapeutics for various human ailments since the origin of life. Bryonia laciniosa (family: Cucurbitaceae) is one such herb, which finds its mention in various traditional systems of medicine and has attracted current researchers due to its significant therapeutic value. OBJECTIVE: The current article aims to present a literature metasynthesis on Bryonia laciniosa. METHODS: The authors performed scholarly searches for peer-reviewed findings on Bryonia laciniosa and incorporated all the data related to the phytochemical and therapeutic profile of the drug. RESULTS: This compilation comprises of Phytochemical and Pharmacological profile of Bryonia laciniosa elaborating its traditional significance and recent researches related to its biological activities. The plant exhibits its potential as an antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsant, anti-asthmatic, anticancer, antioxidant, antidiabetic, and aphrodisiac agent. It also displays its benefits in wound healing and ulcerative colitis. CONCLUSION: The presence of flavonoids, saponins, terpenoids, anthocyanins, coumarins, alkaloids, polyphenols, tannins and emodins in this plant is responsible for its various pharmacological activities. The retrospective study provides direction for existing research as well as future studies to support the domain of pharmaceutical and medical sciences.

Analysis of Active Compounds Using Target Protein Cofilin-Cucurbitacins in Cytotoxic Plant Bryonia cretica.

We examined a two-step target protein binding strategy that uses cofilin as the target protein to analyze the active constituents in Bryonia cretica. In the first step, we prepared the target protein, and used it to analyze the compounds binding to it in the second step. We used the methanolic extract of B. cretica as a library of possible active compounds. We conducted LC-MS analysis using information from our previous study. The peaks in the HPLC profile were identified as cucurbitacin D, isocucurbitacin D, and cucurbitacin I. As far as we know, there is no known study of the activity of isocucurbitacin D in this research field. Therefore, we examined the effects of isocucurbitacin D on cell proliferation and cofilin protein in human fibrosarcoma cell line HT1080 to confirm the effectiveness of this strategy. The cytotoxicity assay, the fibrous/globular actin ratio assay, and the immunoblotting analysis revealed that isocucurbitacin D showed a cytotoxic effect with disruption of target protein cofilin. The target protein binding strategy is a direct and straightforward method for finding new drug seeds from crude sources, such as natural plant extracts.

No effect of a homoeopathic combination of Arnica montana and Bryonia alba on bleeding, inflammation, and ischaemia after aortic valve surgery.

AIMS: " Arnica montana is a popular homoeopathic treatment with potential haemostatic and anti-inflammatory properties. A homoeopathic combination of A. montana and Bryonia alba was used in aortic valve surgery to evaluate its effectiveness in reducing bleeding, inflammation, pain and myocardial ischaemia. METHODS: One day before surgery, 92 adult patients were randomly assigned to a double-blind parallel trial with either homoeopathic granules or a matching placebo until 4 days after surgery. The primary outcome was the volume of blood/liquid in the drains at their removal. The secondary outcomes included postoperative blood/liquid losses at 12 and 24 h as well as C-reactive protein (CRP), pain, temperature and plasma troponin Ic. RESULTS: At 12 h and 24 h after surgery, then at drain removal, blood losses in homoeopathy and placebo groups were not statistically significant (362 +/- 218, 520 +/- 269 and 640 +/- 297 ml vs. 456 +/- 440, 620 +/- 477 and 796 +/- 717 ml; P= 0.19, 0.23 and 0.35, respectively). The statistical modelling did not show significantly different patterns of CRP, troponin and body temperature changes or of pain perception. The number of transfused packed red cells was not significantly different either (P= 0.58). Two patients from each group died during the study period and the number of serious adverse events was not statistically different (six in homoeopathy vs. 10 in placebo groups; Fisher's exact test P= 0.41). CONCLUSIONS: In the study setting, there was no evidence of effects of A. montana and B. alba combination on bleeding, inflammation, pain or myocardial ischaemia.

New cucurbitane-type triterpenoids from Bryonia aspera.

Phytochemical investigation of the chloroform extract of BRYONIA ASPERA roots resulted in the isolation and structure elucidation of two new cucurbitacins (1, 2) together with eight known cucurbitane derivatives (6-13), the pentacyclic triterpene bryonolic acid (5) and two hydroxybenzoic acid amides (3, 4). Their structures were elucidated by spectroscopic analysis, including 2D NMR techniques.

Cucurbitane-type triterpenes with anti-proliferative effects on U937 cells from an egyptian natural medicine, Bryonia cretica: structures of new triterpene glycosides, bryoniaosides A and B.

The 90% aqueous ethanol extract of an Egyptian natural medicine, the roots of Bryonia cretica L., was found to exhibit a strong inhibitory effect on the proliferation of human leukemia U937 cells. By bioassay-guided fractionation, we isolated two new cucurbitane-type triterpene glycosides, bryoniaosides A and B, were isolated from the roots of Bryonia cretica L. together with 16 known cucurbitane-type triterpenes and glycosides. The chemical structures of bryoniaosides A and B were determined on the basis of chemical and spectroscopic evidence. Effects of principal cucurbitane-type triterpenes (cucurbitacins B, D, E, and J, 23,24-dihydrocucurbitacins B and E, and hexanorcucurbitacin D) on proliferation of the cells were examined. Cucurbitacins B and E showed the greater cytotoxic effects with IC(50) values of 9.2 and 16 nM after 72 h, and their IC(50) values were equivalent to that of camptothecin. An alpha,beta-conjugated ketone moiety at the 22-24-positions and an acetoxy group at the 25-position are essential for the strong activity.

A sex-linked SCAR marker in Bryonia dioica (Cucurbitaceae), a dioecious species with XY sex-determination and homomorphic sex chromosomes.

Genetic crosses between the dioecious Bryonia dioica (Cucurbitaceae) and the monoecious B. alba in 1903 provided the first clear evidence for Mendelian inheritance of dioecy and made B. dioica the first organism for which XY sex-determination was experimentally proven. Applying molecular tools to this system, we developed a sex-linked sequence-characterized amplified region (SCAR) marker for B. dioica and sequenced it for individuals representing the full geographic range of the species from Scotland to North Africa. For comparison, we also sequenced this marker for representatives of the dioecious B. cretica, B. multiflora and B. syriaca, and monoecious B. alba. In no case did any individual, male or female, yield more than two haplotypes. In northern Europe, we found strong linkage between our marker and sex, with all Y-sequences being identical to each other. In southern Europe, however, the linkage between our marker and sex was weak, with recombination detected within both the X- and the Y-homologues. Population genetic analyses suggest that the SCAR marker experienced different evolutionary pressures in northern and southern Europe. These findings fit with phylogenetic evidence that the XY system in Bryonia is labile and suggest that the genus may be a good system in which to study the early steps of sex chromosome evolution.

From medicinal plant to noxious weed: Bryonia alba L. (Cucurbitaceae) in northern and eastern Europe.

INTRODUCTION: White bryony, Bryonia alba L., is a relatively little known plant in the history of folk medicine and folk botany in eastern and northern Europe. The main aim of this article is to bring together data about Bryonia alba and to summarise its cultural history and folk botanical importance in eastern and northern Europe. Nowadays, this species is considered at best as an ornamental plant, and at worst as a noxious weed. However, ethnographic and historical sources show that it used to be of magical, medicinal and ritual importance in our part of Europe. METHODS: A diachronic perspective was chosen in order to outline and analyse the devolution and changes in the use of B. alba, in the course of which we take into account the social, ecological and chemical aspects of the usage of this plant. We have therefore traced down and analysed published sources such as ethnographical descriptions, floras, linguistic records and topographical descriptions from northern and central-eastern Europe, particularly Scandinavia, Baltic States, Germany, Poland, Belarus, Ukraine and the Balkan Peninsula. The analysed material is presented and discussed within the biocultural domains that developed in the interaction between human societies and Bryonia alba. RESULTS AND DISCUSSION: Bryonia alba has many folk names in northern and central-eastern parts of Europe: some of them refer to its medicinal properties, life form, odour, or toxicity; others to its possession by the devil. As we learn, Bryonia alba was an inexpensive surrogate for mandrake (Mandragora officinarum L.) and sold as such in the discussed parts of Europe. The folklore and medicinal properties ascribed to mandrake were passed on to white bryony due to an apparent resemblance of the roots. In ethnographic descriptions, we find a mixture of booklore, i.e. written traditions, and oral traditions concerning this species. Some of this folklore must have been an alternative stories spread by swindlers who wished to sell fake mandrake roots to people. CONCLUSIONS: Plant monographs and reviews of particular species tend to concentrate on the botanicals, which might have great useful potential. White bryony presents a precisely opposite example, being a plant that used to be of medicinal relevance and was furnished with symbolical meaning, and has nowadays preserved only its ornamental value among some urban and rural dwellers of northern Europe. Nonetheless, it might be considered as a part of the biocultural heritage in old, well-preserved gardens. It is still used as a medicine in some parts of the Balkan Peninsula.

Bryonia dioica aqueous extract induces apoptosis and G2/M cell cycle arrest in MDA­MB 231 breast cancer cells.

Bryonia dioica Jacq. is a climbing perennial herb with tuberous roots which is widely used in traditional medicine in Algeria for the treatment of cancer. The present study aimed to evaluate the apoptogenic activity and phytochemical composition of the aqueous extract of B. dioica roots growing in Algeria. The cytotoxic effect of B. dioica aqueous decoction against breast cancer MDA­MB­231 cells was evaluated by an MTT assay. Apoptosis induction was assessed by an Annexin V­fluorescien iosthiocyanate assay. Propidium iodide staining of cell DNA was used to assess the effects on the cell cycle. In addition to UV­Visible (UV­vis) analysis, the major compounds of the extracts were determined using liquid chromatography­mass spectrometric analyses. Our results showed that the B. dioica aqueous extract induced cell death in a time­dependent manner. The highest inhibitory effect was produced at concentrations of 50 µg/ml or higher after 72 h of treatment (91.15±0.71%). Furthermore, the extract induced apoptosis of MDA­MB­231 cells. At 250 µg/ml, 64.61% of the treated MDA­MB­231 cells were apoptotic. This was accompanied by cell cycle arrest at G2/M phase. The percentage of cells in G2/M increased from 15.7% (untreated cells) to 59.13% (50 µg/ml) and 58.51% (250 µg/ml). The UV­vis absorption spectra of B. dioica aqueous extract showed two absorption bands characteristic of the flavonol skeleton; 350­385 nm (Band I) and 250­280 nm (Band II). Myricetin (2,5,7,3,4,5­pentahydroxylflavonol) was found to be the major compound in the B. dioica aqueous extract. These findings suggest that B. dioica could be considered a promising source for developing novel therapeutics against breast cancer.

Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract.

OBJECTIVES: The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase-catalysed reactions. METHODS: Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae. KEY FINDINGS: Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed. CONCLUSIONS: Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.

Anthroposophic medicine in the treatment of pediatric pseudocroup: A systematic review.

BACKGROUND: In Europe only few integrative pediatric wards exists and there are two German hospitals focusing on anthroposophic medicine as part of complementary and alternative medicine (CAM). Whilst the most common pediatric diseases are treated here, pseudocroup patients make up a large group in these hospitals, receiving conventional as well as anthroposophic therapies. However, effectiveness of these therapy concepts mostly based on physicians' experiences but clinical studies are hitherto missing. METHODS: A systematic literature search identifying therapy approaches for pseudocroup in children was conducted in general electronic databases (Cochrane Library, PubMed, OVID) and in CAM-specific databases (CAMbase, CAM-QUEST®, Anthromedics). Search results were screened for anthroposophic therapy options. In addition, anthroposophic guidebooks were handsearched for relevant information. RESULTS: Among 157 articles fulfilling search criteria one retrospective study, and five experience reports describing anthroposophic treatments were identified. Several medications for the treatment of pseudocroup were mentioned such as Aconitum, Apis, Bryonia, Hepar sulfuris, Lavender, Pyrit, Sambucus and Spongia. During appropriate use no adverse effects were reported. CONCLUSION: Anthroposophic medicine harbors a broad spectrum of remedies for the treatment of pseudocroup in children. In particular, Aconitum, Bryonia and Spongia are frequently recommended; however, clinical trials investigating the effectiveness are sparse. Therefore, development and validation of therapy strategies are required.

Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.

INTRODUCTION: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. AIM OF THE STUDY: The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, and Bryonia alba. MATERIALS AND METHODS: To investigate the underlying molecular mechanisms of adaptogens, we conducted RNA sequencing to profile gene expression alterations in T98G neuroglia cells upon treatment of adaptogens and analyzed the relevance of deregulated genes to adaptive stress-response signaling pathways using in silico pathway analysis software. RESULTS AND DISCUSSION: At least 88 of the 3516 genes regulated by adaptogens were closely associated with adaptive stress response and adaptive stress-response signaling pathways (ASRSPs), including neuronal signaling related to corticotropin-releasing hormone, cAMP-mediated, protein kinase A, and CREB; pathways related to signaling involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin-angiotensin, AMPK, calcium, and synapses; and pathways associated with dendritic cell maturation and G-coupled protein receptor-mediated nutrient sensing in enteroendocrine cells. All samples tested showed significant effects on the expression of genes encoding neurohormones CRH, GNRH, UCN, G-protein-coupled and other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, transmembrane channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, protein kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, a chaperone (HSPA6), and other proteins, all of which modulate numerous life processes, playing key roles in several canonical pathways involved in defense response and regulation of homeostasis in organisms. It is for the first time we report that the molecular mechanism of actions of melatonin and plant adaptogens are alike, all adaptogens tested activated the melatonin signaling pathway by acting through two G-protein-coupled membrane receptors MT1 and MT2 and upregulation of the ligand-specific nuclear receptor RORA, which plays a role in intellectual disability, neurological disorders, retinopathy, hypertension, dyslipidemia, and cancer, which are common in aging. Furthermore, melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by all adaptogens tested. We conclude that melatonin is an adaptation hormone playing an important role in regulation of homeostasis. Adaptogens presumably worked as eustressors ("stress-vaccines") to activate the cellular adaptive system by inducing the expression of ASRSPs, which then reciprocally protected cells from damage caused by distress. Functional investigation by interactive pathways analysis demonstrated that adaptogens activated ASRSPs associated with stress-induced and aging-related disorders such as chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, metabolic disorders, and cancer. CONCLUSION: This study has elucidated the genome-wide effects of several adaptogenic herbal extracts in brain cells culture. These data highlight the consistent activation of ASRSPs by adaptogens in T98G neuroglia cells. The extracts affected many genes playing key roles in modulation of adaptive homeostasis, indicating their ability to modify gene expression to prevent stress-induced and aging-related disorders. Overall, this study provides a comprehensive look at the molecular mechanisms by which adaptogens exerts stress-protective effects.

A clínica da similitude / The clinical practice of similarity

Agradecemos a gentileza do convite para proferir esta conferência no interessante momento em que, por iniciativa da comissão organizadora deste XXII Congresso Brasileiro de Homeopatia, são convidados observadores e palestrantes da área não homeopática com a intencionalidade de nos questionar e quebrar a assim chamada auto referência. Trazemos aqui algumas considerações sobre a Clínica da Similitude, que esperamos possam contribuir para a compreensão do nosso modelo e levantar questionamentos sobre a nossa prática. Foi-nos ensinado que a ciência começa na filosofia clássica como um projeto de conhecimento do homem, valendo-se inicialmente apenas da razão, incorporando posteriormente o trabalho experimental para a sua evolução e aperfeiçoamento. Nesse contexto observamos que, como consequência do resgate acidental de Hahnemann, a Homeopatia nasce bem dentro da proposta de experimentação buscando, a seguir, valer-se da razão para tentar compreender o conhecimento que ali se mostrava. (AU)

Tratamento homeopático e prevenção da Covid-19: protocolo de pesquisa clínica para avaliar a eficácia e a segurança do medicamento do gênio epidêmico / Homeopathic treatment and prevention of Covid-19: clinical research protocol to evaluate the effectiveness and safety of the epidemic genius medicine

Além da reconhecida aplicação nas doenças crônicas, a homeopatia individualizada também pode atuar de forma resolutiva ou complementar nos casos agudos, incluindo as doenças epidêmicas. No entanto, para atingir esse intento, apresenta uma metodologia semiológica e terapêutica específica que deve ser seguida e respeitada, com o risco de não apresentar a eficácia e a segurança desejada. No caso das doenças epidêmicas, que pela virulência dos seus agentes provoca um quadro sintomatológico comum na maioria dos indivíduos suscetíveis, o medicamento homeopático individualizado (medicamento homeopático do gênio epidêmico) deve apresentar semelhança com o conjunto de sinais e sintomas característicos dos pacientes acometidos nos diferentes estágios de cada surto epidêmico. Estudos evidenciam a eficácia e a segurança desta prática terapêutica e/ou profilática em diversas epidemias do passado. Assim sendo, após o levantamento dos possíveis medicamentos homeopáticos individualizados do gênio epidêmico de cada epidemia, sua aplicação terapêutica e/ou profilática em larga escala deve ser sustentada por ensaios clínicos prévios que demonstrem sua eficácia e segurança, em consonância com os aspectos éticos e bioéticos da pesquisa envolvendo seres humanos. Cumprindo essas premissas da boa prática clínica, elaboramos, em março de 2020, esse protocolo de pesquisa para investigar, em ensaio clínico randomizado, duplo-cego e placebo-controlado, a eficácia e a segurança de possíveis medicamentos homeopáticos individualizados do gênio epidêmico da COVID-19. Caso a eficácia e a segurança se confirmem, e tão somente nessa condição, o medicamento poderá ser utilizado de forma generalizada e coletiva no tratamento e na prevenção da atual epidemia. Com esse intuito, encaminhamos este projeto a médicos, pesquisadores e gestores de diversos hospitais públicos e privados, solicitando uma oportunidade para aplicar essa proposta em pacientes internados em enfermarias e/ou centros de terapia intensiva destinadas ao tratamento da COVID-19.

In addition to the recognized application in chronic diseases, individualized homeopathy can also act in a resolutive or complementary way in acute cases, including epidemic diseases. However, to achieve this intent, it presents a specific semiologic and therapeutic methodology that must be followed and respected, with the risk of not presenting the desired efficacy and safety. In the case of epidemic diseases, which due to the virulence of their agents causes a common symptomatological picture in most susceptible individuals, the individualized homeopathic medicine (homeopathic medicine of the epidemic genius) should present similarity with the set of characteristic symptoms and signs of the patients affected in the different stages of each epidemic outbreak. Studies show the efficacy and safety of this therapeutic and/or prophylactic practice in several epidemics of the past. Therefore, after the survey of possible individualized homeopathic medicine from the epidemic genius of each epidemic, its therapeutic and/or large-scale prophylactic application should be supported by previous clinical trials that demonstrate its effectiveness and safety, in line with the ethical and bioethical aspects of research involving human beings. Fulfilling these premises of good clinical practice, we developed, in March 2020, this research protocol to investigate, in a randomized, double-blind and placebo-controlled clinical trial, the effectiveness and safety of possible individualized homeopathic medicines of epidemic genius of COVID-19. If effectiveness and safety are confirmed, and only in this condition, the medicine may be used in a generalized and collective manner in the treatment and prevention of the current epidemic. To this end, we refer this project to physicians, researchers and managers of several public and private hospitals, requesting an opportunity to apply this proposal to patients hospitalized in wards and/or intensive care units for the treatment of COVID-19.