https://www.healio.com/psychiatry/journals/psycann/1976-12-6-12/{806b8887-c02e-40c8-a228-57f1cdb2bdba}/the-stress-of-life.pdf

The stress of life

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Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives.

Bodily Changes in Pain, Hunger, Fear and Rage

Withania somnifera, also called 'Indian ginseng', is an important medicinal plant of the Indian subcontinent. It is widely used, singly or in combination, with other herbs against many ailments in Indian Systems of Medicine since time immemorial. Withania somnifera contains a spectrum of diverse phytochemicals enabling it to have a broad range of biological implications. In preclinical studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress, neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it has demonstrated the ability to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, and reduce inflammation and enhance endothelial function. In view of these pharmacologic properties, W. somnifera is a potential drug candidate to treat various clinical conditions, particularly related to the nervous system. In this review, we summarize the pharmacologic characteristics and discuss the mechanisms of action and potential therapeutic applications of the plant and its active constituents.

Pharmacologic overview of Withania somnifera, the Indian Ginseng

Background: Withania somnifera is an herbal medicine that has been known to possess memory-enhancing properties. The current study involved an assessment of cognitive and psychomotor effects of Withania somnifera extract in healthy human participants. Materials and Methods : In this prospective, double-blind, multi-dose, placebo-controlled, crossover study, 20 healthy male participants were randomized to receive 250 mg two capsules twice daily of an encapsulated dried aqueous extract of roots and leaves of Withania somnifera or a matching placebo for a period of 14 days. Cognitive and psychomotor performance was assessed pre-dose (day 1) and at 3 hrs post-dose on day 15 using a battery of computerized psychometric tests. After a washout period of 14 days, the subjects crossed-over to receive the other treatment for a further period of 14 days as per prior randomization schedule. Same battery of test procedures were performed to assess cognitive and psychomotor performance. Results: Significant improvements were observed in reaction times with simple reaction, choice discrimination, digit symbol substitution, digit vigilance, and card sorting tests with Withania somnifera extract compared to placebo. However, no effect can be seen with the finger tapping test. Conclusion: These results suggest that Withania somnifera extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment.

Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.

Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus.

Background: Pain affects millions of people worldwide, opioid analgesics have been used for chronic painful conditions. Due to their adverse effects, safer alternatives would be beneficial. Terminalia chebula, with proven analgesic action has been evaluated in the hot air pain model for its analgesic activity. Aim: To evaluate analgesic activity and safety of single oral dose of Terminalia chebula using hot air pain model in healthy human participants. Setting and Design: Randomized, Double blind, Placebo controlled, Cross over study. Materials and Methods: After taking written informed consent to IEC approved protocol, 12 healthy human participants were randomized to receive either single oral dose of two capsules of Terminalia chebula 500 mg each or identical placebo capsules in a double blinded manner. Thermal pain was assessed using hot air analgesiometer, to deliver thermal pain stimulus. Mean Pain Threshold time and Mean Pain Tolerance time measured in seconds at baseline and 180 minutes post drug. A washout period of two weeks was given for cross-over between the two treatments. Results: Terminalia chebula significantly increased mean pain threshold and tolerance time compared to baseline and placebo. Mean pain threshold time increased from 34.06±2.63 seconds to 41.00±2.99 seconds (p<0.001) and mean pain tolerance time increased from 49.67± 3.72 seconds to 57.30±3.07 seconds (p<0.001). The increase in mean percentage change for pain threshold time is 20.42% (p<0.001) and for pain tolerance time is 17.50% (p<0.001). Conclusion: In the present study, Terminalia chebula significantly increased Pain Threshold time and Pain Tolerance time compared to Placebo. Study medications were well tolerated.

Evaluation of the Analgesic Activity of Standardized Aqueous Extract of Terminalia chebula in Healthy Human Participants Using Hot Air Pain Model.

Background: Acute and chronic stress is a risk factor for the development and progression of coronary artery disease. Increased arterial stiffness is an independent marker for cardiovascular disease. Cold pressor test (CPT) is known to be associated with substantial activation of the autonomic nervous system. Objective: The aim of this study was to evaluate the effect of Phyllanthus emblica extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects. Materials and Methods: This was a double-blind, placebo-controlled, crossover study. Participants were randomized to receive either two capsules of P. emblica extract 250 mg (containing aqueous extract of P. emblica, highly standardized by high-performance liquid chromatography to contain low molecular weight hydrolysable tannins emblicanin-A, emblicanin-B, pedunculagin and punigluconin) or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters such as heart rate, augmentation pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and end of treatment. After washout period of 14 days, subjects crossed over to the other treatment and the same test procedure was repeated again. Safety assessments were done at baseline and at the end of treatment. Results: A total of 12volunteers completed the study. Compared with baseline and placebo, P. emblica extract produced a significant decrease of mean percent change in the indices of arterial stiffness (AIx, radial and aortic BP) and increase in SEVR, an index of myocardial perfusion with CPT. Both treatments were well-tolerated and no serious adverse events were reported. Conclusion: Proprietary P. emblica extract, showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections.

Evaluation of Phyllanthus emblica extract on cold pressor induced cardiovascular changes in healthy human subjects.

Background: The Stroop paradigm evaluates susceptibility to interference and is sensitive to dysfunction in frontal lobes and drug effects. The aim of the present study was to establish a simple and reliable computerized version of Stroop color-word test, which can be used for screening of various psychotropic drugs. Materials and Methods: The standardized method was followed in all cases, by recording the reaction time (RT) in msec in 24 healthy participants using computerized version of Stroop color-word test. Reproducibility of the test procedure was evaluated by recording the RTs by a single experimenter on two sessions (interday reproducibility). Validity of the model was further tested by evaluating the psychotropic effect of Zolpidem 5 mg, Caffeine 500 mg, or Placebo on 24 healthy subjects in a randomized, double blind three-way crossover design. Results: The method was found to produce low variability with coefficient of variation less than 10%. Interday reproducibility was very good as shown by Bland-Altman plot with most of the values within ±2SD. There was a significant increase in RTs in Stroop performance with Zolpidem at 1 hr and 2 hrs; in contrast, caffeine significantly decreased RTs in Stroop performance at 1 hr only compared to placebo. Conclusion: The Stroop color-word recording and analysis system is simple, sensitive to centrally acting drug effects, and has potential for future experimental psychomotor assessment studies.

Usharani Pingali

Papers

Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.

Study of pharmacodynamic interaction of Phyllanthus emblica extract with clopidogrel and ecosprin in patients with type II diabetes mellitus.

Evaluation of the Analgesic Activity of Standardized Aqueous Extract of Terminalia chebula in Healthy Human Participants Using Hot Air Pain Model.

Evaluation of Phyllanthus emblica extract on cold pressor induced cardiovascular changes in healthy human subjects.

A computerized stroop test for the evaluation of psychotropic drugs in healthy participants.