Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT-IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharma...

https://www.tandfonline.com/doi/pdf/10.1080/10717544.2016.1212950

Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats

Withania somnifera Dunal is an Indian medicinal plant with significant pharmacological properties, such as adaptogenic, anti-inflammatory, anti-oxidant, anti-platelet, anti-hypertensive, hypoglycemic and hypolipidemic effects. Several chemotypes of W. somnifera include NMITLI-101, NMITLI-118 and NMITLI-128. The present work elaborates the optimization and development of a liposomal delivery system for efficient delivery of NMITLI118RT+ [a standardized ethanolic extract of a new chemotype of W. somnifera Dunal (NMITLI-118) roots] against cerebral stroke in rats. Liposomal systems were prepared using thin-film hydration method and characterized on the basis of size, zeta potential, physical stability, FT-IR, DSC-TGA analysis and surface morphological studies by TEM. NMITLI118RT+ and its formulations (NMITLI118RT+LF) were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. The Z average of the developed liposomal formulation was about 142.6 ± 0.09 nm with a zet...

https://www.tandfonline.com/doi/pdf/10.3109/10717544.2015.1041579

Neuro-protective potential of a vesicular system of a standardized extract of a new chemotype of Withania somnifera Dunal (NMITLI118RT+) against cerebral stroke in rats.

Rutin, a natural flavonol glycoside is known to possess significant radical scavenging properties which might have beneficial effects in cerebral ischemia. However its oral administration and pharmaceutical use is limited due to its poor aqueous solubility and bioavailability. The current investigation aimed at development of rutin–phospholipid complexes (Ru–PLC's) and its characterization to provide neuro-protective effects in brain injury following stroke. Ru–PLC's were successfully fabricated and findings demonstrated improvement in bio-pharmaceutical properties on the basis of solubility, partition coefficient, dissolution profile, morphology, zeta potential, physical stability, FT-IR, DSC-TGA, forced degradation, photolytic degradation, ROS detection and oral pharmacokinetic studies. Ru–PLC's considerably improved functional outcomes in experimental stroke (MCAO model in rats) at a dose less than half of the effective dose of rutin. Effectiveness of treatment as evident from pharmaceutical properties as well as therapeutic activity was of the following order: Ru–EPLC > Ru–TPLC > rutin.

Rutin phospholipid complexes confer neuro-protection in ischemic-stroke rats

Medicinal plants are highly important for producing structurally unique phytomolecules that possess diverse pharmaceutical and commercial significance In this chapter, various modern molecular approaches are discussed to improve medicinal plants, using Ashwandha (Withania somnifera) as an example, wherein tremendous progress has happened during the last decade or so W somnifera, commonly known as Ashwagandha, possesses wide therapeutic repute due to the presence of signature phytochemical withanolides (C-28 steroidal lactone-based compounds) In-depth study of biochemical pathways and regulation is an important area of research owing to the wide range of medicinal properties of withanolides The enzymes involved in the early biosynthetic process of withanolides have been characterized to some extent With recent developments in next-generation sequencing during the last decades, the identification of novel enzymes involved in the modification of the withanolide backbone has taken place In this chapter, we summarize the biosynthetic pathway and characterize the genes/enzymes of the pathway along with the in vitro developments associated with withanolide production The information is useful in defining the plants as well as in developing newer plants with promising pharmacological and agrotechnological traits

Improving medicinal crops through phytochemical perspective: Withania somnifera (Ashwagandha)

Withania somnifera Dunal (Ashwagandha), is an Indian medicinal plant with significant pharmacological properties. Withanolides (steroidal lactones) are the chief constituents potentially responsible for its activity. Some of its chemotypes includes NMITLI-101, NMITLI-118, NMITLI-128. The present work elaborates the optimization and development of a ready to fill capsule powder blend (NMITLI118RT+CFM) for efficient delivery of NMITLI118RT+ (a standardized extract of a new chemotype of Withania somnifera Dunal) and to investigate their protective effects against cerebral stroke in rats. NMITLI118RT+CFM was prepared by solid liquid compacting technique and filled into capsules; it was characterized on the basis of loss on drying, flow properties, IR, disintegration time, weight variation, content uniformity and DSC analysis. NMITLI118RT+ and NMITLI118RT+CFM were evaluated for biological activity utilizing middle cerebral artery occlusion model in rats. NMITLI118RT+CFM was found to be pharmaceutically acceptable. Results showed that NMITLI118RT+ and NMITLI118RT+CFM possess significant neuroprotective activity against cerebral ischemia at 50 mg kg−1 in rats. NMITLI118RT+ and its pharmaceutical compositions exhibit sufficient biological promise for management of cerebral stroke. The investigation discloses potent and prudent therapeutic potential of a new formulation using standardized fraction of a new variety of Withania somnifera (NMITLI118RT+) for brain function restoration and protection from neurological failures.

Enduring protection provided by NMITLI118RT+ and its preparation NMITLI118RT+CFM against ischemia/reperfusion injury in rats

Background: Withania somnifera Dunal (Ashwagandha) is an Indian medicinal plant of great medicinal value; used in many clinically proven conditions. NMITLI-118RT+ is a candidate drug under a Council of Scientific and Industrial Research (CSIR) networking project. It is a chemotype of W. somnifera's root extract, which has been used for the present study. Objectives: The present investigation aims to develop and validate a simple isocratic reverse phase-high performance liquid chromatography (RP-HPLC) system for the detection and estimation of Withanolide A (marker compound) and its analytical application for stability indicating studies on NMITLI-118RT+. Material and Methods: A validated RP-HPLC method for Withanolide A was established on a Waters HPLC system and the same was used on NMITLI-118RT+ for quantification and fingerprinting purposes, and for establishing forced degradation, isothermal stress tests, and drug-excipient testing protocols as per International Conference on Harmonization (ICH) guidelines. Results: A validated method was established, which could detect the marker at a retention time of around 6.3 minutes, with a linearity range of 2-100 μg/mL, by varying the amounts of the said marker, which were estimated in four different batches of NMITLI-118RT+. Photostability as per ICH guidelines suggested a slight loss of the active constituent and maximum degradation was afforded with alkali followed by acid, and then peroxide, in the forced degradation studies. In the drug-excipient studies, the maximum amount of active constituent could be detected in the samples with ethyl cellulose and the least with hydroxy propyl cellulose. Conclusion: The method developed here was simple and rapid. The various stability indicating studies carried out in the present investigation would be useful for formulation development and were suggestive of deciding the recommended storage conditions for NMITLI-118RT+.

Rajender Singh Sanghwan

Papers

Stability indicating studies on NMITLI 118RT+ (standardized extract of withania somnifera dunal).