Shatavari

Asparagus Racemosus (called Shatavari in Ayurveda where it is established as Rasayana) is a herb that has historical usage as a treatment for dyspepsia and gastric ulcers as well as being used as a galactogogue (promotes lactation),^[1] the latter being similar to Ayurvedic usage of Fenugreek. The roots of the herb are used, and are known to be bittersweet and have also been reported to be used in Siddha and Unani medicine.^[2]

Other properties generally attributed to the roots are emollient (moisturizing), cooling, nervine tonic, constipating, galactogogue, aphrodisiac, diuretic, rejuvenating, carminative, stomachic, and antiseptic.^[1][3]

It belongs to the plant family Asparagaceae with Asparagus being the plant genus, and aside from Racemosus two other species are sometimes used for medicinal purposes; adscendens and gonaclades.^[1] This plant family consists of well over 300 species spread amongst temperate and tropical regions.^[4]

The plant that is commonly eaten as a vegetable is the species Asparagus Officinalis,^[5] and may not possess the same bioactivities as Asparagus Racemosus.

Asparagus Racemosus is a herbal medicine that is related to but is not the commonly eaten vegetable; same genus but different species

Asparagus Racemosus roots (main supplemental source) tends to contain:

• Shatavarin IV,^[6] a steroidal saponin (8.53+/-0.38%)^[2] and Shatavarin I; both of which are seen as the main bioactives^[7][4]
• Shatavaroside C^[6]
• Shatavarol^[6]
• Immunoside at 0.038+/-0.003%,^[2] this is a glycoside of Sarsasapogenin^[8]
• Racemoside A,^[6] also found in the fruits^[9]
• Daidzein (one of the two soy isoflavones) at 57.8mcg/100g^[10]
• Secoisolariciresinol at 68.4mcg/100g^[10]
• Ursolic Acid^[6]
• Beta-Sitosterol and Stigmaterol^[6]
• A small ecdysteroid content^[11]
• Vitamin C at 42.4+/-5.1mg/100mL basic extract^[12]
• Minerals, such as Zinc (44-148mg/kg), Copper (up to 34mg/kg), Manganese (up to 84mg/kg), Iron (up to 2g/kg), and Cobalt (sometimes up to 122mg/kg, mostly undetectable)^[13]

Unprocessed Asparagus Racemosus may have an Inulin content (dietary fiber).^[14]

Shatavarin and the Shatavarosides are commonly seen as the main bioactive components of Asparagus Racemosus, although other compounds may also be bioactive

While the fruits contain:

• Racemoside A, B, and C^[9]
• Sarsasapogenin, the aglycone of Racemosides A-C^[9]

In general, the total flavonoid content of Asparagus Racemosus (roots) tends to be 36.7+/-3.9mg/100mL and the polyphenolic content being 88.2+/-9.2mg/100mL; Asparagus Racemosus does not show a good antioxidant profile in vitro.^[12]

It should be noted that Asparagamine A, also known as Didehydrostemefoline,^[15] does not exist in Asparagus Racemosus. It was initially named Asparagamine A due to the plant it was isolated from initially thought to be Asparagus Racemosus,^[16] but it properly belongs to the plant Stemona japonica^[17] and other plants of the Stemonaceae family.^[16] One study assessing Asparagus Racemosus products on the market has confirmed a lack of Asparagamine A in this plant.^[18]

'Asparagamine A', better known as Didehydrostemefoline, was mistakenly thought to exist in Asparagus Racemosus but has since been noted to not possess this compound despite the name

Asparagus Racemosus has shown some anti-depressant effects as assessed by Forced Swim Test and Learned Helplessness when a concentrated extract (62.2% saponins) is given at 100-400mg/kg possibly via serotonergic mechanisms, as 5-HTP induced head twitches were enhanced while L-DOPA induced hyperactivity was not.^[19] This may be mediated by MAO inhibition;^[20] Asparagus Racemosus does not appear to favor either subset preferentially, and inhibits both MAO-A and MAO-B with an IC₅₀ of 11.72+/-0.82mg/mL and 14.70+/-0.93mg/mL, respectively. Inhibition of both MAO enzymes is competitive, and significantly weaker than the standard drugs used (Moclobimide and Selegeline).^[20]

Other studies have been conducted on Asparagus and Depression, but are confounded with other nutrient inclusions; Perment (Ashwagandha, Bacopa Monnieri, and Clitoria Ternatea) was used in one study^[21] and Siotone (Ashwagandha and Holy Basil) in another.^[22]

May have putitative anti-depressive effects, but there is no indication that these are potent nor any evidence in humans at this moment in time

Asparagus Racemosus appears to have pro-cognitive effects at 50-200mg/kg related to the cholinergic system,^[23] which may be related to acetylcholinesterase inhibiting activity.^[20] When tested in vitro, a saponin extract of Asparagus has an IC₅₀ value of 12.35+/-1.16mg/mL on acetylcholinesterase inhibition; this was significantly less potent than the standard drug Galantamine (0.30+/-0.01mg/mL).^[20] Some inhibitory actions were also seen on Butyryl cholinesterase with an IC₅₀ value of 15.92+/-1.57mg/mL, and significantly less potent than the standard drug Physostigmine (0.09+/-0.01);^[20] all inhibition appears to be competitive, and in vivo it appears to be dose dependent.^[23]

The aforementioned learning study used a 62.2% saponin content methanolic extract, and noted that all concentrations tested (50, 100, 200mg/kg) were effective in increasing spatial memory at similar potencies to 500mg/kg Piracetam, used as a reference drug, with no dose-dependence being noted with Asparagus treatment.^[23]

Appears to have nootropic properties at relatively low doses, via acetylcholinesterase inhibition

The ethanolic extract of Asparagus Racemosus was fed to rats at 100, 200, and 400mg/kg who were then subject to stress tests (restraint, swimming endurance, and chemical-induced stress).^[24] Asparagus produced anti-stress effects in a dose-dependent manner, but was less potent than 2mg/kg Diazepam; with Diazepam being 7% more effective than 400mg/kg Asparagus Racemosus.^[24] Asparagus Racemosus at 100mg/kg was less effective than 100mg/kg Ashwagandha in reducing the effects of restraint stress, but became more potent when the dose was increased to 400mg/kg.^[24]

One study of physical stress (5 hours of constant swimming in mice) noted that corticosterone levels in serum, used as a biomarker of stress, were unable to be significantly reduced by either the aqueous or methanolic extracts of Asparagus Racemosus. The active control of Panax Ginseng reduced the stress-induced increase by 25.6% but was significantly outperformed by both Chlorophytum arundinaceum and Asparagus adscendens, able to reduce levels of corticosterone below resting control.^[25]

Appears to have moderately potent anti-stress effects in rats, but is outclassed by other compounds

Asparagus Racemosus ethanolic extract appears to reduce glucose absorption (as evidenced by faster transit time and reduced serum glucose AUC) in the intestines of rats and inhibited sucrase activity (approximately 25%) after an oral dose of 1250mg/kg taken alongside carbohydrates.^[26]

In vitro usage with the ethanolic extract of Asparagus Racemosus appears to induce glucose uptake into 3T3-L1 adipocyte independent of glucose, but has the uptake rate significantly enhanced when insulin is introduced into the medium.^[26]

Over 28 days of feeding to rats at 1250mg/kg, the ethanolic extract appears to increase serum insulin levels by 30%.^[26] This was thought to be secondary to direct influences on pancreatic Beta-cells.^[27]

At oral doses between 6.25-200mg/kg, administration of Asparagus Racemosus to mice orally for a week prior to exposure to an antigen was able to upregulate the percentage of T-Cells expressing CD3⁺ and CD4⁺/CD8⁺ positive cells, suggesting T-cell activating potential in a dose dependent manner with best results at 100mg/kg bodyweight. At this dose and compared to the active control of Levamisole (2.5mg/kg), Asparagus Racemosus was able to enhance total T-Cells 31.5% above control, T-Helper cells by 23.7%, and Cytotoxic T-Cells by 19.7%; all three parameters underperformend relative to Levamisole being 90.9%, 88.4%, and 85.4% as potent, respectively.^[2] A saponin was isolated from the EtOAc extract that, at doses of 1, 3, or 10mg/kg was more effective than the whole Asparagus Racemosus extract at the aforementioned doses, but still underperformed 2.3mg/kg Levamisole.^[28] Oral administration of Asparagus Racemosus has been noted to be beneficial elsewhere.^[29]

Another study assessing Immunoside (Sarsasapogenin glycoside) as an adjuvant noted that while the active control of Aluminum salts (0.5mg/mL) increased the efficacy of the antibody response (HBsAg) by 1.3-fold that Immunoside at 3, 10, and 30mcg increased the response 1.69, 2.03 and 2.79 fold, although 100mcg decreased response; a similar degree of response was seen after 15 and 28 days sensitization.^[8] While aluminum oxide increased splenocyte proliferation by 24%, these three doses of Sarsasapogenin increased proliferation by 43%, 72% and 158%, and 30mcg/mL was significantly more effective than Aluminum on prolierating CD3, CD19, and CD4/8 cells.^[8]

May potentiate the body's response to antigens, similar to Panax Ginseng which has been suspected for having a role as adjunct therapy alongside vaccination

The aqueous extract of Asparagus Racemosus was able to enhance peak levels of Natural Killer (NK) Cells by 16.9+/-4.4% (5.6mcg/mL) yet when it was controlled for the polysaccharide content the increase in NK Cells was 51.8+/-1.2% (25mcg/mL) in human PBM cells.^[30] Both appeared to be somewhat bioactive at the low concentrations of 0.2mcg/mL, and the fructooligosaccharides were 8% more effective than the positive control of Protein bound polysaccharide (PSK).^[30]

Appears to have the ability to enhance NK cell levels at concentrations that may be biologically relevant

Asparagus Racemosus is traditionally known as belonging to a genus of phytoestrogenous plants,^[4] and Asparagus Racemosus was once implicated in estrogenic effects in a rat uterotrophic assay using the brand name Menosan, which was confounded with other herbs such as Saraca Indica and Glycyrrhiza glabra; this study was conducted by the company producing the supplement combination (Himilaya).^[31]

Asparagus (Officinalis) does appear to possess a Secoisolariciresinol lignan content,^[32][10] and its diglucoside form does possess estrogenic effects;^[33] it has further been argued that this content may apply to Asparagus Racemosus due to the species of the Asparagus genus not being genomically diverse.^[4] However, no conclusive evidence exists for a connection between Asparagus Racemosus per se and estrogenic actions.

Currently insufficient evidence to implicated Asparagus Racemosus for increasing estrogen

A water-soluble extract of Asparagus Racemosus, when fed to male rats at a dose of 200mg/kg bodyweight, was able to increas testicular size slightly (6.8%, possibly secondary to increased spermatogenesis^[34]) and increased attraction towards females rats approximately twofold; this was of equal efficacy when compared to Curculigo orchioides and slightly lesser than Chlorophytum borivilianum which reached 2.5-fold.^[35] All herbs (200mg/kg) outperformed 0.5mg/kg of testosterone injected twice weekly.^[35]

Mounting Latency was reduced by 32% in Asparagus Racemosus treated animals, and the Intromission Latency and Penile Erectile Index were reduced by 31% and increased 143%, respectively.^[35] Intromission frequency increased, while mounting and ejaculation frequency trended to increase but failed to be significant; on all parameters Asparagus was outperformed Chlorophytum borivilianum.^[35] This improvement in erections has been noted elsewhere with 100mg/kg,^[34] and was again outperformed by C.Borivilianum.

Appears to possess some aphrodisiac properties

In a rat model of ulcerogenesis, a basic extract of Asparagus Racemosus at 100mg/kg appeared to be effective in reducing both stress-induced and Indomethacin (NSAID)-induced ulcers, but more effective at the latter.^[36] This was later replicated with Indomethacin, where 100mg/kg Asparagus Racemosus was noted to reduce gastric acid secretion with a protective effect similar to 30mg/kg of Ranitidine Hydrochloride.^[37]

One study assessed a variety of chemical-induced ulcers and noted protection at 100mg/kg against alcohol-induced ulcers (11.8%), Cysteamine-induced ulcers (85.3%), Aspirin ulcers (75.1%), and Pyloris Ligation induced ulcers (93.6%).^[38] Protection was dose dependent in all situations except alcohol (where protection was poor at all tested concentrations) and outperformed the reference drug sucralfate (250mg/kg) in all conditions except alcohol-induced ulcers.^[38]

Appears to have moderately potent anti-ulcer activity, but no human studies have been conducted; oddly, may not work against alcohol-induced ulcers

One study in rats assessing intestinal motility noted that 150, 200, and 250mg/kg of Asparagus Racemosus (aqueous or ethanolic extract) both showed efficacy in reducing how long castor oil (used to induce diarrhea) acted, exerting anti-diarhhoeal effects of similar potency.^[39] In a test on general intestinal transit speed compared against atropine (0.1mg/kg; IP injection used as a positive control) the ethanolic extract at 200mg/kg was 86% as effective as atropine while the aqueous extract was 22.5% as effective; both were less effective, however.^[39]

May possess anti-diarrhoeal effects and slow intestinal transit

Asparagus Racemosus is one of the few herbs that has potential to influence lactation, alongside Fenugreek and Milk Thistle.^[40]

Asparagus Racemosus (AR) ethanolic extract appears to have a degree of efficacy in protecting against kidney stones at highers doses (800 and 1600mg/kg),^[41] and exerted a protective effect against ethylene-glycol induced kidney stones.^[42]

May reduce kidney stone formation, unknown practical relevance

Asparagus Racemosus also appears to possess diuretic properties, which are attributed to it historically.^[43] This diuretic effect has been noted in rats given multiple doses of Asparagus Racemosus, but showed most significance at the highest dose (3200mg/kg), where urine output was increased 36.8% while the control drug furosemide (25mg/kg) increased urination by 60.5%.^[44]

Possesses a diuretic effect, but appears to only be significant at higher doses

100-250mg/kg ethanolic extract for 4 weeks after diabetes is induced in rats (streptozotocin) shows moderate protective effects on the kidneys, attenuating adverse changes in oxidative markers (MDA, enzmyes) and creatinine.^[45] A renoprotective effect has also been noted in a study on urolithiasis, where creatinine levels induced by treatment were attenuated significantly with high dose (800, 1600mg/kg) ethanolic extract Asparagus Racemosus alongside less histological damage.^[41]

One study has assessed the anti-oxidative ability of Asparagus Racemosus on the liver of rats noted that 50mg/kg of Asparagus Racemosus was able to attenuate damage induced by Isoniazid, a medication causing toxic symptoms in some patients. Isoniazid appears to induce CYP2E1 which mediates toxicity^[46] and may be secondary to depletion of glutathione s-transferases;^[47] Asparagus appears to attenuate the increase in CYP2E1 to 86% of toxin-control yet appeared to have more significant protective effects on liver enzymes, which were reduced to increases of 40% (ALP), 21.6% (ALT), and 38.4% (AST), assuming toxin-control is 100%.^[48] These were thought to be secondary to antioxidative properties of Asparagus Racemosus.

In animal interventions, doses of up to 2500mg/kg of the water extract^[2] and 2000mg/kg of the ethanolic extract appear to be well tolerated.^[41]

One study using a methanolic extract of 100mg/kg for 60 days appeared to exert teratogenic effects to rat pups.^[49]