The research work carried out by CSIR-IIIM featuring the role of Crocus sativus-Based Botanical Lead IIIM141 for the potential of management of Alzheimer’s Disease (AD), could be one more step in Alzheimer’s disease prevention & management.
AD is a chronic neurodegenerativedisorder of complexetiology with progressive neuronal damageresulting in dementia symptoms. Due to the complex etiology of the disease, the researchers promote the polypharmacology/multiple targetapproach for the management of AD.
The research group at CSIR-IIIM, Jammu, INDIA have come up with interesting results while working with ‘Crocus sativus’(saffron). They have identified a lead chemical entity (IIIM-141) that showed unique properties to protect the brain cells and delay the onset of neurodegenerative diseases during the preclinical animal testing.
The developed extract was found to be efficacious in in vitro and in vivo assays of dementia and AD and was found to be safe as per OECD Guidelines for the Testing of Chemicals. Also, the newly developed sustained release (SR) capsule formulation showed superiority over the conventional formulation.
The research says:
“With the increased life expectancy, age-related neurodegenerative diseases like Alzheimer’s and dementia (memory loss) have emerged as the new global public health challenges. The number of patients with Alzheimer’s disease is rising around the globe.The hydroalcoholic extract of C. sativus stigma (IIIM-141) was studied for its chemical standardization (with five chemical markers), quality control (for aflatoxin/pesticide content and microbial load), in vitro efficacy in multiple targets, in vivo efficacy in anti-dementia models, acute/subacute toxicity in rodents, and preparation of the oral dosage form
The group of crocins and their aglycone metabolite, crocetin, are mainly responsible for pharmacological activities associated with saffron. The administration of the saffron extract along with the food has resulted in a decreased load of amyloid-β, upregulation of synaptic proteins, and reduced neuroinflammation in the brains of experimental animals.
Also, A sustained release (SR) capsule formulation was developed, which showedan improved in vitro dissolution profile and a significantly enhanced plasma exposure in the pharmacokinetic study. The SRformulation resulted in 3.3-fold enhancement in the area under the curve of crocetin and doubling of thecrocetin/crocin ratioin plasma compared with the extract.
What could be the possible future?
Since, theacute oral toxicity study shows that IIIM-141is safe up to the dose of 2000 mg/kg, with no effect on the body weight and on biochemical/hematological parameters ofthe rats. Also, the repeated oral administration of IIIM-141 for 28 days at 100 mg/kg dose did not cause any preterminal deaths andabnormalities in Wistar rats, it is evident that the preclinical data presented herein warrant its clinical investigation. This data serves as the benchmark for further research on this botanical product.
The study was done by a research group at CSIR-IIIM and has been published in ACS Omega “Preclinical Development of Crocus sativus-Based Botanical Lead IIIM-141 for Alzheimer’s Disease: Chemical Standardization, Efficacy, Formulation Development, Pharmacokinetics, and Safety Pharmacology
Sonali S. Bharate, Vikas Kumar, Gurdarshan Singh, Amarinder Singh, Mehak Gupta, Deepika Singh, Ajay Kumar, Ram A. Vishwakarma, and Sandip B. Bharate
ACS Omega 2018 3 (8), 9572-9585”
“Earlier, Director, IIIM said the US Food and Drug Administration approved the product as a dietary supplement. Now there are plans to carry out clinical trials in association with a US-based company in order to bring out a medicine using the same chemical.
‘Also, the nutraceutical would be launched in the US market as a dietary supplement in October-November. It would be available in the form of an oral capsules that people with more than 40 years of age need to be taken twice a day. After another six months, the product would come to India,’ IIIM director Ram Vishwakarma told Deccan Herald” -DH
CSIR-IIIM, Jammu has licensed a technology on a Saffron based nutraceutical product for brain health to Pharmanza Herbal Pvt. Ltd., Gujarat on 3rd July, 2018 for launching this product both in domestic and US market.