PHARMACEUTICAL STANDARDIZATION OF ASTERCANTHA LONGIFOLIA KSHARA

Objective: The present study was aimed for establishment of SMP (standard manufacturing procedure) of Astercantha longifolia (A. longifolia) kshara and to develop its quality control parameter. Methods: The kshara was prepared as per the AFI (Ayurvedic Formulary of India) guideline and for the purpose of standardization three batches were prepared and its mean and standard deviation was calculated. Results: In the present study it was discovered that the average percentage yield of 3 batches of A. longifolia kshara obtained from a completely dried whole plant 0.81% w/w. Physico-chemical analysis of powder showed foreign matter to be less than 1% w/w, loss on drying 27.5 % w/w, total ash less than 9%, acid insoluble ash to be less than 1%, water soluble extractive value and alcohol soluble extractive value as 10.78% w/w and 5.45 % w/w respectively and pH to be 7.3 which is in accordance with quality standards to be preserved, also Physico-chemical parameters applied to kshara reveals loss on drying as 13.35% w/w and pH to be slightly basic in nature i.e., 7.93. Conclusion: Many references in the classics are mentioned regarding the preparation of kshara; however, as per the findings of the present study, it might be concluded that this method is the standard method to get the maximum yield of A. longifolia kshara

New Uncertainties in QCD-QED Rescaling Factors using Quadrature Method

In this paper we briefly outline the quadrature method for estimating uncertainties in a function of several variables and apply it to estimate the numerical uncertainties in QCD-QED rescaling factors. We employ here the one-loop order in QED and three-loop order in QCD evolution equations of fermion mass renormalization. Our present calculations are found to be new and also reliable compared to the earlier values employed by various authors.Comment: 14 page

Probing the seesaw mechanism with neutrino data and leptogenesis

In the framework of the seesaw mechanism with three heavy right-handed Majorana neutrinos and no Higgs triplets we carry out a systematic study of the structure of the right-handed neutrino sector. Using the current low-energy neutrino data as an input and assuming hierarchical Dirac-type neutrino masses $m_{Di}$, we calculate the masses $M_i$ and the mixing of the heavy neutrinos. We confront the inferred properties of these neutrinos with the constraints coming from the requirement of a successful baryogenesis via leptogenesis. In the generic case the masses of the right-handed neutrinos are highly hierarchical: $M_i \propto m_{Di}^2$; the lightest mass is $M_1 \approx 10^3 - 10^6$ GeV and the generated baryon-to-photon ratio $\eta_B\lesssim 10^{-14}$ is much smaller than the observed value. We find the special cases which correspond to the level crossing points, with maximal mixing between two quasi-degenerate right-handed neutrinos. Two level crossing conditions are obtained: ${m}_{ee}\approx 0$ (1-2 crossing) and $d_{12}\approx 0$ (2-3 crossing), where ${m}_{ee}$ and $d_{12}$ are respectively the 11-entry and the 12-subdeterminant of the light neutrino mass matrix in the basis where the neutrino Yukawa couplings are diagonal. We show that sufficient lepton asymmetry can be produced only in the 1-2 crossing where $M_1 \approx M_2 \approx 10^{8}$ GeV, $M_3 \approx 10^{14}$ GeV and $(M_2 - M_1)/ M_2 \lesssim 10^{-5}$.Comment: 30 pages, 2 eps figures, JHEP3.cls, typos corrected, note (and references) added on non-thermal leptogenesi

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Standard operating procedure of Hingulottha Parada

Parada (mercury) is an important ingredient of Ayurvedic drugs particularly of the Rasayogasi.e. metallic and mineral formulations. According to the classical texts Hingulottha Paradahas similar properties to Ashtasamskarita Parada. Generally Parada is collected by UrdhvaPatana (upward sublimation), Adhah Patana (downward sublimation), and Tiryanka Patana(transverse sublimation) method from the Hingula (cinnabar) i.e. HgS. There are so manymethods with same principles which are found for the extraction of Parada from Hingula. Butmost of the methods are not convenient to procure Parada from Hingula. Considering this, apharmaceutical study has been taken up on extraction of Parada from Hingula by Nadayantramethod. Average yield of 73.00% Hingulottha Parada was obtained in this study

ASHVAGANDHADHYA GHRITA-A CLASSICAL FORMULATION IN A NEW PERSPECTIVE PROPERTIES

Ashvagandha (Withania somnifera) is an important drug of Ayurvedic therapeutics. It is found almost all over India and the part used chiefly is root. This root smells like horses urine and so the name - Ashvagandha. Due to its multiple beneficial properties it is known as Indian ginseng. Somnifera in Latin means sleep inducing implicating its calming effect. Ashvagandhadhya Ghrita is a classical formulation stated in chapter of Vata Vyadhi in the text Chakradutta. It is prepared with ingredients- Ashvagandha Kvatha (decoction), Ashvagandha Kalka (paste), Go-dugdha and Go-ghrita. The individual ingredients of this formulation have Rasayan, Medhya etc. properties. Rasayan means that which promotes physical and mental health, helps to increase the bodys capacity to overcome diseases and diverse stress factors. It also enhances longetivity. Today, on similar line is concept of adaptogen- that which helps the body to face better the situations which produce stress and its related effects in body. Medhya means which is beneficial for intellect and memory. Moreover this is a formulation of Sneha Kalpana containing Ghrita as its base. It is known that blood brain barrier allows lipid soluble drugs to easily pass into the brain and thereby act on central nervous system. Thus looking to properties of individual ingredients and Kalpana (dosage form) it is hypothesized that the formulation as a whole also would have Rasayan i.e., adaptogenic and memory enhancing effect whereby it would be useful in conditions ranging from stress to anxiety to neurodegenerative diseases like Alzheimers disease etc

Fuzzy Set Qualitative methodology for identifying the Critical Process Parameters and Quality attributes in the manufacturing of Arogyavardhini Rasa

The traditional drug manufacturing process involves numerous qualitative attributes that directly impact product quality. The Process Analytical Technology approach considers that to enhance process control, identifying critical process parameters and critical quality attributes that affect the manufacturing process is very much necessary. The Ayurvedic drug manufacturing process is more driven by fuzzy qualitative attributes. The present study was executed to identify the Critical Process Parameters and Critical Quality Attributes in the manufacturing process of a herbo-mineral formulation, viz. Arogyavardhini Rasa. Fuzzy set Qualitative Comparative Analysis (fsQCA) methodology was adopted to observe and identify the critical parameters. The study was executed in three steps, viz. Data collection, Data arrangement, and Analysis. The raw data collected was arranged and analyzed in the software R studio using the package QCA in four steps, viz. Calibration, Analysis of Necessity and Sufficiency, Truth Table construction, and Minimization. The results obtained show that Size reduction, Mardana, and Drying are the identified Critical Process Parameters that, in combination, lead to the outcome, i.e., good product quality. Thus, this study proves that Fuzzy Set Qualitative Comparative Analysis can be used as an efficient tool for the identification and measurement of the Critical Process Parameters that affect the Critical Quality Attributes and, thereby, the product quality in the manufacturing of Arogyavardhini Rasa