Acute and subacute oral toxicity evaluation of Ayurvedic formulation Tapyadi loha in rats.

Ayurveda is one of the oldest systems of traditional medicine that provides treatments for a wide range of acute and chronic health problems. It is a common myth amongst people that Ayurvedic drugs have no side effects, whereas the fact is that these drugs can cause adverse effects. Despite their wide use, the safety data of many Ayurvedic formulations are still unavailable. Tapyadi loha is an Ayurvedic formulation traditionally claimed for iron deficiency anemia in pregnant and non-pregnant patients. However, no scientific study has been conducted to evaluate its oral toxicity. Hence, the present study evaluated the acute and subacute oral toxicity of the Tapyadi loha according to the OECD test guidelines 425 and 407, respectively. Tapyadi loha did not cause mortality nor any signs of toxicity when given once orally at a dose of 2000 mg/kg. Subacute toxicity study showed no mortality as well as no behavioral, hematological, biochemical and histopathological abnormalities in rats treated with Tapyadi loha formulation at 250, 500 and 1000 mg/kg for 28 days. It is concluded that the Tapyadi loha is safe at a single dose of 2000 mg/kg and 28 days repeated dose of 1000 mg/kg by oral route in rats.

Five years of disease-free survival in a case of recurrent, post-op, grade 3, stage 2, Malignant Spindle Cell Melanoma treated with Ayurvedic medicines: A case report.

Malignant spindle cell melanoma is a rare cancer with a questionable prognosis because of limited published case reports. This article discusses a male patient with a history of Spindle cell melanoma tumor, Rt heel, Grade 3 (Gr 3) Stage 2 (St 2) seen in our OPD treated with supporting herbo-mineral combination of Ayurvedic medicine. Such types of cancers are of concern and can be more troublesome to the patient. The initial chief complaint of the patient was a palpable corn-like growth in the right heel, which was surgically removed at that time. When it recurred after one year, it was investigated thoroughly and it was found malignant, and then operated again. The patient came to us after his second operation. After appropriate analysis based on Ayurvedic and modern parameters, the patient was treated with Ayurved treatment. As there was no other treatment suggested by oncologists, he was on supportive Ayurvedic treatment only. Ayurvedic treatment continued for 2 years afterwards. The treatment module showed complete relief in the symptoms (100%), by the end of treatment. Follow-up PET scans showed further improvement and a complete reversal of residual disease was observed. The last PET scan did not show any evidence of abnormality. To date, there has been no recurrence and the patient has been living completely normally for the last almost 5 years (karnofsky score 90/100). It can be concluded that the addition of Ayurvedic treatment might have helped this patient of malignant spindle cell melanoma for regression of residual disease, prevention of metastasis to date, and a good quality of life. We have observed 5+ years of disease-free survival and near-normal quality of life for this patient, and still ongoing.

Integrating network pharmacology and in silico analysis deciphers Withaferin-A's anti-breast cancer potential via hedgehog pathway and target network interplay.

This study examines the remarkable effectiveness of Withaferin-A (WA), a withanolide obtained from Withania somnifera (Ashwagandha), in encountering the mortiferous breast malignancy, a global peril. The predominant objective is to investigate WA's intrinsic target proteins and hedgehog (Hh) pathway proteins in breast cancer targeting through the application of in silico computational techniques and network pharmacology predictions. The databases and webtools like Swiss target prediction, GeneCards, DisGeNet and Online Mendelian Inheritance in Man were exploited to identify the common target proteins. The culmination of the WA network and protein-protein interaction network were devised using Stitch and String web tools, through which the drug-target network of 30 common proteins was constructed employing Cytoscape-version 3.9. Enrichment analysis was performed by incorporating Gprofiler, Metascape and Cytoscape plugins. David compounded the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and enrichment was computed through bioinformatics tools. The 20 pivotal proteins were docked harnessing Glide, Schrodinger Suite 2023-2. The investigation was governed by docking scores and affinity. The shared target proteins underscored the precise Hh and WA network roles with the affirmation enrichment P-value of <0.025. The implications for hedgehog and cancer pathways were profound with enrichment (P < 0.01). Further, the ADMET and drug-likeness assessments assisted the claim. Robust interactions were noticed with docking studies, authenticated through molecular dynamics, molecular mechanics generalized born surface area scores and bonds. The computational investigation emphasized WA's credible anti-breast activity, specifically with Hh proteins, implying stem-cell-level checkpoint restraints. Rigorous testament is imperative through in vitro and in vivo studies.

Eleven years of disease free survival in a case of Invasive Ductal Carcinoma (IDC) Rt Breast grade 3, stage 3, treated with add on Ayurveda treatment: A case report.

Breast cancer shows high mortality, especially in women worldwide. This report discusses a case of female patient with a history of Invasive Ductal Carcinoma (IDC) Rt Breast, ER, PR negative, Grade 3 (Gr3) Stage 3 (St3) seen in our OPD treated with supporting herbo-mineral-metallic combination of Ayurveda medicines. Generally, breast cancers of such subtype and that too in Lower Outer Quadrant (LOQ) are always of a concern and can be more troublesome to the patient. When the patient came for the first time, her chief complaint was palpable lump in her right breast for previous three months. We advised her to undergo relevant investigations and, it was found to be malignant. She underwent surgery, Modified Radical Mastectomy,(MRM), followed by chemotherapy. During chemotherapy, which was Adriamycin + Cyclophosphamide (AC) protocol 4 cycles, followed by Docetaxel 4 cycles, every 21 days. After 2 cycles, she started complaints of pain in both calf regions, numbness in fingers of hand and foot, severe generalized skin rash with itching, hyperacidity and constipation. She visited our clinic again for the same, and Ayurveda treatment was started to her at this point. So, at the time of commencement of treatment, the diagnosis was "IDC Rt Breast, LOQ, Gr3 St3, ER, PR negative HER2Neu positive, post op, on chemo". After appropriate analysis based on Ayurvedic and modern parameters, she was diagnosed to have vitiation of Rakta and Pitta (Dushti avastha), due to cyto-toxic nature of (Visha exposure) chemotherapy and medication was planned accordingly, along with chemotherapy protocol. The Ayurveda treatment showed significant relief in the chemotoxicity symptoms, within one month and she could tolerate further chemotherapy cycles very conveniently. On completion of chemotherapy, she was diagnosed to have need of good immunity (Vyadhi-Kshamatva). Based on this diagnosis, Ayurveda treatment protocol was changed and this new regimen continued for almost 6 years afterwards. Laboratory and imaging investigations performed periodically showed marked improvement, and even currently not showing any abnormality. Till date, there is no recurrence and patient is living completely normally for last 11 years. As all the symptoms and investigations showed near complete improvement; it may be concluded that probably add on Ayurveda treatment (Integrative approach) proved effective in this patient of IDC. We have observed 11 years of disease-free survival and excellent quality of life in this patient and still ongoing.

An in-silico investigation and network pharmacology based approach to explore the anti-breast-cancer potential of Tecteria coadunata (Wall.) C. Chr.

Uncontrolled cell proliferation is a common definition of cancer. After lung carcinoma, breast neoplasm is the second-most prevalent kind of cancer. The majority of breast cancer cells and healthy breast cells both have receptors for circulating oestrogen and progesterone. In order to promote the development and division of cancer cells, oestrogen and progesterone bind to the receptors and may collaborate with growth factors (such as oncogenes and mutant tumour suppressor genes). As per the literature, Tecteria coadunata (Wall.) C. Chr. has anticancer, antioxidant and anti-inflammatory potential. After the hydroalcoholic extraction of this rhizome, total of 200 phytochemicals were retrieved from HR-LCMS analysis. In this current study, Network pharmacology was carried out to explore the rationale of Tecteria coadunata (Wall.) C. Chr. by using different database using Cytoscape software. The network depicted the interaction of Bioactives with their targets and their association with several disease, especially breast cancer. Tecteria coadunata (Wall.) C. Chr. has offered new relationship with variety of genes and its applications in different types of breast cancers. Further Gene Ontology was carried out and it showed key targets were TP53, BRCA2, PGR and CHEK 2. Further Signalling pathways were also enriched. Flex-X software was used for molecular docking studies, and it verified that Dopaxanthin, Dantrolene and Orotidin shows the highest binding affinities with key targets. Additionally, Pharmacokinetic analysis revealed that all top three lead compounds which follows the Lipinski Rule (Rule of three) without interrupting the conditions of bioavailability with minimal toxicity.Communicated by Ramaswamy H. Sarma.