Table 4.
Anti-depressant effects of Ashwagandha (Withania somnifera, WS) in animal studies.
| Nature of Extract, Standardization | Dosage | Model | Behavioral Effects | Biological Effects | Refs. | ||||
|---|---|---|---|---|---|---|---|---|---|
| Aqueous methanolic (40:60) root and leaf extract (AME), withanolide-rich fraction from AME (WF), flavonoid-rich fraction from AME (FF), compound isolated from WF (Withanoside X), Enteric-coated versions (EC-AME, EC-WF, EC-FF, EC-WX) | AME, WF, FF: 60mg/kg p.o. Withanoside X: 10mg/kg p.o. EC-AME: 20mg/kg p.o. EC-WF: 15mg/kg p.o. EC-Withanoside X: 2.5mg/kg p.o. All WS treatments given 4 hrs prior to assessment |
Rat (reserpine) | ▼depression-like behavior (FST) | Not assessed | [120] | ||||
| Withanolide-free root extract | 3.3, 10, 33.3, and 100 mg/kg p.o. for 12 days | Rat (stress) | ▼depression-like or anxiety-like behavior (MBT) | ▼stress-induced weight loss ▼stress-induced increase in rectal temperature ▼transient hyperthermic response ▼stress-induced increase in adrenal weight ▼stress-induced increase in plasma cortisol and blood glucose |
[54] | ||||
| Methanolic root extract, standardized to 2.7% (w/w) total withanolides | 10, 20, and 40 mg/kg/day p.o. for 11 days, or as a single dose | Rat (stress) | ▼depression-like behavior (TST) ▲reaction time (HPT) |
▼stress-induced weight loss ▼transient hyperthermic response (FSS) |
[51] | ||||
| Traditional root extract (Ashwagandha ghrutha) consisting of root:ghee:water (1:4:16) | 20 and 40 mg/kg, given 1 hr prior to assessment (acute) or for 7 days (chronic); Route of administration NR | Mouse | ▼ depression-like behavior (TST, 40 mg/kg acute or 20 and 40 mg/kg chronic WS dosing; FST, 20 and 40 mg/kg chronic WS dosing) ▲ antidepressant activity of low-dose imipramine (FST, TST, 10 mg/kg each, acute or chronic dosing) ▼reserpine-induced catatonia and sedation (ART) alone (20 and 40 mg/kg WS) and in combination with low-dose imipramine 10 mg/kg each) all at chronic dosing |
▼reserpine-induced ptosis (ART), alone (20 and 40 mg/kg) and in combination with low-dose imipramine (10 mg/kg each) all at chronic dosing | [117] | ||||
| Powder, NR | 50, 100 and 150 mg/kg p.o. for 2 weeks | Rat | ▼depression-like behavior (LHT, FST) ▲antidepressant activity of low-dose imipramine (LHT, FST, 16 mg/kg imipramine, 50 mg/kg WS) |
Not assessed | [118] | ||||
| Root extract, NR | 50, 100, 200, or 500 mg/kg p.o. on days 38-42 of social isolation and 1 hr prior to assessment | Rat (social isolation) | ▼depression-like behavior (FST) ▼anxiety-like behavior (EPM) ▲anti-anxiety action of diazepam at subtherapeutic dose (50 mg/kg) of WS (EPM) |
Not assessed | [78] | ||||
| Root extract, NR | 25, 37.5, 50, 100 and 200 mg/kg i.p., 30mins before assessment | Mouse (untreated, clonidine, reserpine) |
▼depression-like behavior (FST; 50 to 200 mg/kg WS) ▲imipramine and fluoxetine antidepressant activity at subtherapeutic dose (37.5 mg/kg) of WS (FST) ▼reserpine- and clonidine-induced depression-like behavior (FST; 100 mg/kg WS) |
Not assessed | [119] | ||||
| Nature of Extract, Standardization | Dosage | Model | Behavioral Effects | Biological Effects | Refs. | ||||
| Glycowithanolide-rich fraction (containing sitoindosides VII-X and withaferin) isolated from aqueous ethanolic (1:1) root extract, standardized to 28-30% withanolide glycosides | 25 and 50 mg/kg p.o. for 21 days, administered 1 hr before assessment | Rat (chronic stress) | ▼depression-like behavior (FST, LHT) ▼stress-induced memory impairment (EPM, PAT), sexual behavior inhibition (FSS) |
▼stress-induced hyperglycemia, perturbed glucose tolerance test, and gastric ulcers (FSS) ▼stress-induced immunosuppression (FSS) |
[52] | ||||
| Glycowithanolide-rich fraction (WSG, containing sitoindosides VII-X and withaferin) isolated from aqueous root extract, standardized to 1.13% total steroid content | 20 and 50 mg/kg p.o. for 5 days | Rat | ▼depression-like behavior (LHT, FST) ▼anxiety-like behavior (EPM, SIT, NSFLT) |
▼PTZ-induced increase in rat brain tribulin activity (PTZ) | [81] | ||||
| Sitoindosides VII and VIII | PTZ, FST: 20 mg/kg i.p., 30 mins prior to assessment FST: 20 and 50 mg/kg i.p., 30 mins prior to assessment OST, TCT: 50 mg/kg p.o. for 4 days RST: 50 and 100 mg/kg p.o. for 4 days; 100 mg/kg i.p., 30 mins before morphine administration Morphine toxicity: 50 mg/kg p.o. for 4 days |
Mouse, rat (stress) | ▼depression-like behavior (FST) ▼anxiety-like behavior (PTZ-induced) |
▼stress-induced autoanalgesia, gastric ulcers (RST) ▼morphine-induced hypothermia (RST) ▼morphine toxicity (OST, TCT) ▼tribulin activity in urine (RST) ▲stress-induced decrease in adrenal content of ascorbic acid, corticosterone |
[17] | ||||
▲ – Increased; ▼ – Decreased; ART = Anti-reserpine test; EPM = Elevated plus maze test; FSS = Foot shock stress test; FST = Forced swim test; HPT = Hot plate test; LHT = Learned helplessness test; NR = Not reported; NSFLT = Novelty-suppressed feeding latency test; OST = Overcrowding stress test; PAT = Passive avoidance test; PTZ = pentylenetetrazol administration; RST = Restraint stress test; SIT = Social interaction test; TCT = Tactile stress test; TST = Tail suspension test.