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. 2020 Jun 29;12(7):1935. doi: 10.3390/nu12071935

Table 11.

Literature studies on the effect of hempseed or hempseed products’ dietary supplementation on animal models.

Supplement Type Purpose Experimental Design Results Ref.
Hempseed meal hydrolysate (HMH) Evaluation of the antioxidant ability of an HMH-containing diet to attenuate the plasma levels of some oxidative stress markers in growing and adult SHRs rats. 8-week old SHRs (n = 8) fed control or 1% HMH-containing diets ad libitum for 8 weeks (for analysing the preventive effect).
20-week old SHRs (n = 4) fed control or HPH-containing diets ad libitum for 4 weeks (for analysing the treatment effect).
Dietary intervention with a specific HMH on young and adults SHRs exerted an antioxidant action by:
• The increase of the SOD and CAT activities in both growing and adult SHRs;
• The significant decrease of the TPx plasma level in both growing and adult SHRs and NTRs.
[117]
Hempseed Investigation of the aspects of dietary hempseed against hyperlipidemia-associated CV risks. 1 month of 10% hempseed supplemented high fat-diet on Wistar rats. The 10% hempseed dietary treatment had an anti-hyperlipidaemic effect by inducing:
• The serum level decreases of the cholesterol, LDL and triglycerides;
• The increase of the HDL serum level;
• A significant reduction in the aorta thickness;
• Less intima damage foam cells formation and smooth muscle cell proliferation;
• The remarkable decrease in the lipid deposition, plaque size, and lesion surface area distribution;
• The decrease of the pro-inflammatory PGEs expression;
• The increase of the anti-inflammatory PGDs expression.
[131]
Hempseed Evaluation of the effect of hempseed feeding on lipid and protein profiles. 20-days of hempseed supplementation (free access) on Wistar rats. Short-term hempseed dietary intake can have hepatoprotective properties and beneficial effect on the prevention of CVD by favouring:
• The decrease of the mean fasting serum LDL level;
• The increase of the mean fasting serum HDL and total protein levels.
[132]
Hempseed water extract (HWE) Evaluation of the anti-atherosclerotic activity of hempseed water extract in ApoE KO mice. 14-days of intragastric inoculation of 300 µL of hempseed water extract or distilled water (control) to six-week-old, male ApoE KO (n = 7). Dietary HWE ingestion exerted an anti-atherosclerotic effect through:
• The reduction of the atherosclerotic plaque formation in the aortic sinuses;
• The reduction of the serum GOT concentration, demonstrating less liver damage after the treatment;
• The decrease of total serum cholesterol and LDL, and the increase of serum HDL;
• The significant decrease of TNF-α serum level.
[133]
Hempseed Meal (HSM) Investigation of the protective effects of the dietary intake of HSM and its LA and ALA components on AD and CVD Drosophila melanogaster models. GMR-Aβ42 Drosophila melanogaster line (AD model) reared in cornmeal-soybean standard media with the LA, ALA, and GLA amounts present in the HSM (for the effect on AD phenotype).
Wild-type Drosophila melanogaster larvae reared in HSM media with 35.1 μg/mL of cholesterol (for the CV effect).
Thanks to their LA and ALA contents, HSM dietary uptake may exert beneficial effects on AD and CVD through:
• The suppression of suppressed Aβ42 cytotoxicity in the GMR-Aβ42 flies’ line reared on HSM mean (beneficial effect on AD);
• The reduction of dietary cholesterol uptake observed in the wild-type flies reared on the cholesterol media (beneficial effect on CVD).
[134]
Hempseed Investigation of the ability of dietary hempseed to reduce platelet aggregation under hypercholesterolemia. Male New Zealand rabbits fed 125 g/day of control diet supplemented with 10% of hempseed and 0.5% of cholesterol for 8 weeks. Hempseed supplementation to a hypercholesterolemic diet is able to normalize the platelet aggregation by increasing the GLA plasma level. [135]
Hempseed Investigation of the dietary hempseed ability to inhibit atherosclerosis and the associated vascular contractile dysfunction in a cholesterol-induced rabbit model. Male albino New Zealand rabbits fed 125 g/day of control diet supplemented with 10% of hempseed and 0.5% of cholesterol (to induce atherosclerotic plaque formation) for 8 weeks. Dietary hempseed supplementation did not generate protection against atherosclerotic plaque formation in hypercholesterolemic diet, but it provided mildly beneficial effects against contractile dysfunction associated with atherosclerotic vessels. [136]
Hempseed Investigation of the ability of hempseed dietary intake on the prevention of ovarian hormone deficiency-induced hypercholesterolemia in ovariectomized rats and on the complications of estrogen deficiency such as depression, anxiety, and bone loss problems. Bilateral ovariectomized six-month-old female Wistar rats (n = 5) fed 1%, 2%, or 10% hempseed supplemented diets or a control diet (standard commercial diet) for 3 weeks. Until 10% of hempseed dietary supplementation improved the post-ovariectomized complications in rats since it:
• Prevented the accrual of blood calcium, preventing the bone loss;
• Prevented the body weight gain induced by ovariectomy;
• Conserved the TGs and TC plasma levels as those of the non-ovariectomized rats, preventing dyslipidaemia;
• Resulted in an antidepressant activity.
[137]
Hempseed meal hydrolysate (HMH) Evaluation of the effect of HMH-containing diet on the prevention and treatment of hypertension in growing SHRs and in SHRs with established hypertension. 8-week old SHRs (n = 8) fed control or 1% HMH-containing diets ad libitum for 8 weeks (for the preventive effect).
20-week old SHRs (n = 4) fed control (without HPH) or HPH-containing diets, ad libitum for 4 weeks (for analysing the treatment effect).
Dietary intervention with a specific HMH on young and adult SHRs exerted a preventive and therapeutic effects since it led to:
• The attenuation of the normal increases of SBP in young growing SHRs;
• The significant reduction of SBP in adult SHRs;
• The significant reduction of the plasma ACE and renin activities in both young and adult SHRs.
[138]
Hempseed and bitter vegetable (HB) Evaluation of the beneficial effect of the HB diet on chronic diseases and on the slowing of the aging process. 15-month-old C57BL/6 female mice (n = 10) fed low CHO, low SFA, and high PUFA content-HB diets containing hempseed and bitter vegetable (Sonchus oleraceus) (2:1) or control (western diet), ad libitum until only 20% of the mice in one group survived. The HB diet is capable of promoting health and longevity since it:
• Significantly increased the mice lifespan;
• Improved the spatial learning and memory, and the locomotory activity;
• Exerted beneficial effects on hepatic steatosis, hepatotoxicity, and plasma lipid profiles including the normalization of the size, weight, and colour of the liver and the reduction of hepatic lipid accumulation and of the ALT, AST, and TG levels.
• Provided protective effects against the aging-related abnormalities in spleen morphology and inflammation;
• Increased the antioxidant defences and decreased the oxidative stress;
• Decreased the systemic inflammation by lowering the plasma level of the inflammatory cytokines (i.e., TNF-α, IL-1β, MCP-1 and IL-6), and by increasing the plasma level of anti-inflammatory IL-10;
• Improved the gut microbiota profile leading to a significant decrease in the gut levels of E. coli and a significant increase in the gut levels of Bifidobacterium and Lactobacillum species after 11 weeks of dietary intervention;
• Increased the sensitivity to insulin;
• Increased the hepatic expression of genes associated with longevity (i.e., AMPK, Sirt1, Nrf-1, and FOXO3).
[140]
Hempseed oil and Evening primrose oil (HSO/EPO) Evaluation of the MS’ therapeutic effect of co-supplementation with HSO/EPO. 14 days of HSO/EPO oral administration on adult female C57BL/6 (n = 6) EAE mice (MS model) The HSO/EPO dietary treatment can exert a beneficial effect on MS treatment since it is able to:
• Act as an immunomodulator, down-regulating the mRNA expression of mTORC1 (which promotes Th1 and Th2 cells differentiation) and of the pro-inflammatory cytokines IFN- in lymph node;
• Exert an anti-inflammatory action through increasing the mRNA expression of mTORC2 (which promotes Th2 cells differentiation) and of the anti-inflammatory cytokines IL-10 in lymph nodes;
• Reduce the infiltration of the inflammatory cells in brain;
• Promote the re-myelination of neurons’ myelin sheath.
[140,141]

ACE: angiotensin I-converting enzyme; AD: Alzheimer Disease; ALA: α-Linolenic Acid; ALT: Alanine Transaminase; AMPK: AMP-activated protein kinase; ApoE KO: Apolipoprotein E Knockout; AST: Aspartate Aminotransferase; CAT: Catalase; CHO: Carbohydrate; CVD: Cardiovascular Disease; EAE: Experimental Autoimmune Encephalomyelitis; FOXO3: Forkhead box O3; GLA: γ- linolenic acid; GOT: glutamic oxaloacetic transaminase; HDL: High Density Lipoprotein; IFN-γ: Interferon γ; LA: Linoleic Acid; LDL: Low Density Lipoprotein; MCP-1: Monocyte Chemoattractant Protein 1; MS: Multiple Sclerosis; mTORC1: mTOR Complex 1; mTORC2: mTOR Complex 2; rf-1: Nuclear respiratory factor 1; NTRs: Normotensive Rats; PGD: Prostaglandin D; PGE: Prostaglandin E; PUFA: Polyunsaturated Fatty Acid; SBP: Systolic Blood Pressure; SFA: Saturated Fatty Acid; SHRs: Spontaneously Hypertensive Rats; Sirt1: Sirtuin 1; SOD: Superoxide dismutase; TC: Total Cholesterol; TG: Triglyceride; IL: Interleukin; TGs: Triglycerides; TNF-α: Tumor Necrosis Factor α; TPx: Total Peroxide.