Withania somnifera Extracts Promote Resilience against Age-Related and Stress-Induced Behavioral Phenotypes in Drosophila melanogaster; a Possible Role of Other Compounds besides Withanolides

Abstract

Withania somnifera (WS) extracts have been used in traditional medicine for millennia to promote healthy aging and wellbeing. WS is now also widely used in Western countries as a nutritional supplement to extend healthspan and increase resilience against age-related changes, including sleep deficits and depression. Although human trials have supported beneficial effects of WS, the study designs have varied widely. Plant material is intrinsically complex, and extracts vary widely with the origin of the plant material and the extraction method. Commercial supplements can contain various other ingredients, and the characteristics of the study population can also be varied. To perform maximally controlled experiments, we used plant extracts analyzed for their composition and stability. We then tested these extracts in an inbred Drosophila line to minimize effects of the genetic background in a controlled environment. We found that a water extract of WS (WSAq) was most potent in improving physical fitness, while an ethanol extract (WSE) improved sleep in aged flies. Both extracts provided resilience against stress-induced behavioral changes. WSE contained higher levels of withanolides, which have been proposed to be active ingredients, than WSAq. Therefore, withanolides may mediate the sleep improvement, whereas so-far-unknown ingredients enriched in WSAq likely mediate the effects on fitness and stress-related behavior.

Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster

“…Cohorts of 10–20 flies were then aged on food vials with vehicle alone, with supplemental CAW, or with compounds for a total of 10 days, with fresh food being provided at day 5. The stress paradigm was initiated at day 10 with repetitive phases of 300 Hz vibrations with cohorts of 10–20 flies confined to empty, narrow tubes during daytime (usually 8 am to 6 pm), as described earlier [ 23 , 24 ]. The stress application was given for three consecutive days, unless indicated otherwise, with flies being transferred to a fresh food vial with or without the supplement overnight.…”

“…The post-stress tests (T1) were performed after the three days of stress application, unless indicated otherwise, after a short resting period on standard food after the last stress application. An attempt to climb the gap was defined by the stereotypical leg-over-head behavior [ 23 , 24 ].…”

“…Flies were collected and subjected to the same feeding and stress protocol as outlined above. After the final day of stress application, flies were placed in empty vials to deprive them of food for at least 8 h. The S4S paradigm was performed as described in Ries et al [ 23 , 24 ]. Briefly, individual flies were confined to a 55 × 20 mm 2 chamber made of a 3 mm thick white foam board.…”

“…Drosophila melanogaster flies have long been used as a model to investigate biological processes, including complex behaviors [ 18 , 19 ]. Drosophila has also served as a relatively easy system to test drugs and other compounds, including adaptogens used in traditional Asian medicine [ 20 , 21 , 22 , 23 ]. We have recently established a model to induce a depression-like state in Drosophila by exposing them to chronic, uncontrollable stress [ 24 , 25 ].…”

Ashwagandha (Withania somnifera) - influence on sleep: review

“…wykazały wydłużenie całkowitego czasu snu oraz skrócenie czasu potrzebnego do zaśnięcia bez negatywnego wpływu na aktywność motoryczną podczas okresu czuwania owadów poddanych działaniu witanii ospałej [11]. Pozytywny wpływ na sen muszek Drospophilia potwierdzono również w badaniu przeprowadzonym przez Holvoet H et al (2022) [19].…”