In female subjects, the risk of coronary heart disease and other CVDs related to the rise of the concentration of circulating total cholesterol and LDL-cholesterol, can also increase as a consequence of menopause, which is associated also to other relative complications related to the estrogen deficiency, like depression, anxiety, and possibly impaired cognition. In this context, Saberivand and colleagues  demonstrated that whole hempseeds dietary supplementation (until 10%) in a balanced diet of the ovariectomized rat model of menopause, may improve the menopausal complications including the cardiovascular ones. In particular, the authors have shown that 3 weeks of dietary supplementations with 1%, 2%, or 10% of hempseeds were able to conserve the triglycerides and total cholesterol plasma level close to the control group (non-ovariectomized rats), preventing the dyslipidemia and the weight gain that usually occurs after ovariectomy (or menopause) as a consequence of the decline of the estrogen levels. Indeed, it was found that the decline of plasma estrogen levels was prevented by the hempseeds dietary treatment, probably thanks to the presence of phytoestrogens, such as β-sytosterol, in hempseeds. In addition, the authors even observed that the hempseeds dietary supplementation was also capable of exerting an antidepressant activity, as well as of preventing the accrual of blood calcium and thus preventing the bone loss and promoting the bone homeostasis.
Regarding MUFAs and SFAs, literature publications agree that the MUFAs content, mainly OA, decreased with the increase of the level of the hempseed products to the diet, probably due to the inhibition effect of a PUFAs-rich diet on the activity of ∆-9 desaturase, which is essential for the conversion of PA to OA [150,153,155,157]. Whereas, about the effect on SFAs there are some contrasting results. Some authors found a reduction in the SFAs [155,158], as well as in the cholesterol amount  in egg yolk after hempseed supplementation. Other researchers [153,157] showed that the overall levels of SFAs and cholesterol of egg yolk were not influenced by a dietary treatment with hempseeds, hempseed oil, or hempseed cake.
Data are expressed as mean ± standard deviation. n.a.: not available.
House and colleagues  investigated the in vivo digestibility of hempseed proteins using a rat bioassay for protein digestibility, with the aim to evaluate the actual amino acid bioavailability. The authors observed that the in vivo protein digestibility of hempseed proteins collocates hempseed in the same range as the major pulse protein sources, such as lentils, and above cereal grain products. Furthermore, they also found that the presence of hull in the seed negatively affects the digestibility of the hempseed proteins. In fact, removal of the hull fraction from the hempseed led to an average increase in the protein digestibility from 85.2 to 94.9%. The authors supposed that the high fibre content of the hull may exert an influence on the digestibility of the proteins, but it is also possible that this decrease is, almost in part, due to the presence of some antinutritional factors such as phytate and trypsin inhibitors [39,74,75], with a different distribution in the various parts of the whole hempseed (see Section 3.1.5).
3.2.2. Hempseed Bioactive Peptides
As said, another bioactive property attributed to hempseed protein hydrolysate was the anti-hypertensive activity . Publications investigating the structural features of the hydrolysate’s component peptides found that most bioactive peptides able to inhibit renin and/or ACE contained three or four amino acids and some particular structural characteristics related to its sequence. They had a good hydrophobicity/hydrophilicity balance; contained hydrophobic amino acids at the C-terminal, aromatic, or branched-chain amino acid residues near the C-terminal; and hydrophobic residues at the N-terminal. Moreover, when a branched-chain, hydrophobic amino acid residue and/or an ionizable functional group were present at the N-terminal or near it, the ACE-inhibitory activity may be enhanced [121,123,124,125]. Hempseed peptides with these structural features that has been shown to possess in vitro ACE-inhibitory activity were the Glycine-Valine-Leucine-Tyrosine (GVLY), Leucine-Glycine-Valine (LGV) , Tryptophan-Valine-Tyrosine-Tyrosine (WVYY), and Proline-Serine-Leucine-Proline-Alanine (PSLPA) peptides, whereas the peptides Tryptophan-Tyrosine-Threonine (WYT), Serine-Valine-Tyrosine-Threonine (SVYT), and Isoleucine-Proline-Alanine-Glycine-Valine (IPAGV) showed dual inhibition of ACE and renin enzymes , with the tripeptide WYT exhibiting the strongest renin inhibition related to the presence in its sequence of the main structural features characteristics of renin-inhibitor peptides, namely one hydrophobic side chain (tryptophan) at the N-terminal, bulky chains (tyrosine) at the C-terminal, one hydrogen bond donor (tryptophan), and two hydrogen bond acceptors (threonine and tyrosine) . Girgih and colleagues  found that the hempseed peptides inhibited ACE through a mixed-type model of enzyme inhibition, implying that peptides bound to both active and non-active sites, thus blocking the substrate binding or producing changes in the enzyme’s conformation, which reduced the substrate affinity with the active site. These interactions between peptide and ACE were mainly stabilized by electrostatic and hydrophobic interactions and hydrogen bond formation. Whereas the hempseed peptides inhibited renin enzyme by an uncompetitive model of enzyme inhibition, implying that peptides bound to the renin−substrate complex, causing reduction in the reaction velocity as well as the catalytic efficiency. Also in this case, the main involved interactions were the electrostatic and hydrophobic ones, as well as multiple hydrogen bonds. Of note, these bioactive peptides originated by simulated gastrointestinal digestion of hempseed proteins. In addition, the in vivo hypotensive ability of the WVYY, PSLPA, WYT, SVYT, and IPAGV peptides were assessed after oral administration of 0.5 mg/mL of each peptide to spontaneously hypertensive rats. The results demonstrated that all analysed peptides were able to significantly reduce the systolic blood pressure (SBP) of animals, but PSLPA, SVYT, and IPAGV exerted a long-lasting SBP-lowering effect, indicating a more efficient absorption coupled with strong binding to target enzymes and resistance to structural inactivation by gastrointestinal tract or blood circulatory system proteases .
Phytic acid is a natural plant compound acting as the major storage form of P as well as the primary P reserve for the plant. Indeed, it constitutes 60 to 70% of the total P in cereal grains, oilseeds, and legumes and generally comprises 1–5% weight in cereals, oilseeds, legumes, and nuts . From a chemical point of view, PA is a myo-inositol hexakisphosphate (IP6) composed by an inositol ring esterified with six phosphate groups that are not internally connected; hence it has up to 12 replaceable protons allowing it to bind with multivalent cations (i.e., Zn 2+ , Fe 2+/3+ , Ca 2+ , Mg 2+ , Mn 2+ , and Cu 2+ ), positively charged proteins, and in some cases, starch through hydrogen bonds , forming insoluble complexes known as phytates. Both phytate-mineral and phytate-protein complexes are not readily absorbed by monogastric animals including humans because of their inability to metabolize phytic acid due to the lack of a sufficient level of phytate-degrading enzymes in their digestive tract. Thus, these complexes negatively affect the bioavailability of dietary and endogenous minerals and proteins as well as the digestive enzymes’ activity; therefore, for these reasons, phytic acid is considered an antinutrient. However, phytic acid may also have beneficial effects in the prevention and treatment of several pathological conditions related to oxidation and cancer , maybe due to its ability to chelate Fe ions, that lead phytic acid to inhibit iron-driven hydroxyl radical (–OH • ) formation and, hence, to strongly suppress lipid peroxidation and the oxidation of other biomolecules. Hence, for optimum physiological benefit of phytic acid, the phytate content in the upper part of the gut should be low to avoid negative effects on mineral and protein absorption and bioavailability, but at the same time, it should be high enough to use its antioxidant and anticancer activity. However, to date, accurate and clear information on the phytate dosage required to elicit beneficial effects in human is still limited. In accordance with Russo and Reggiani , to increase the safety for feed and food formulation, it is preferable to reduce the phytic acid content to at least 0.45 g/100 g of defatted sample. According to literature data, the results obtained by different authors about the phytic acid content in hempseed ( Table 8 ) are in good agreement and show that the level of this antinutritional compound ranges between 4 and 8% of the dry weight of the defatted matter. Galasso and colleagues  found a significant variability in the phytate content among different hemp cvs, and Russo  showed that French monoecious varieties had lower content than Italian dioecious ones, but this evidence is exactly the opposite of what Galasso and co-workers  found analysing twenty hempseed cvs and accessions of different origin, among which, the French varieties have been to be those with the highest phytic acid content. These differences in the results could be explained by the significant influence of genotype, growing year and the interaction between these two factors on the antinutritional compounds’ amount, phytic acid included . Compared to other seeds, the content of phytic acid in hempseed seems to be higher. For example, Russo and Reggiani, and Russo and co-workers [73,75] highlighted that the phytic acid content of hempseed was higher than those found in soy bean (2%), and Mattila and colleagues , comparing different type of oilseed, legumes, and pseudo-cereal grains, observed that oilseeds in general, including hempseed, linseed, and rapeseed, form a group with a higher phytic acid content in comparison to other legumes (e.g., fava bean and lupin) and pseudo-cereal grains (e.g., quinoa and buckwheat), and among the analysed oilseeds, whole hempseed was that with the highest phytic acid level.
Hence, although different evidence of an effective beneficial action of hempseeds or hempseed derivatives on CVDs and neurodegenerative disease animal models is present in scientific literature ( Table 11 ), further studies are still needed to clarify the exact molecular mechanisms involved as well the type and the doses of the more efficient hempseed product necessary to exert the in vivo beneficial function, that are all essential factors to develop a potentially functional food.
Together with phenolic compounds, other kinds of hempseed’s functional compounds are the bioactive peptides. The evidence of the existence of these peptides has been demonstrated by the findings about the bioactive features observed for the products obtained by the hydrolysis of hempseed proteins. Indeed, it has been shown that, although hempseed proteins have limited bioactive properties, their hydrolysis provides hydrolysates with higher bioactivity [112,113,114], including antioxidant [72,112,113,114,115,116,117,118], antihypertensive [114,119], antiproliferative [72,112], hypocholesterolemic [120,121], anti-inflammatory, and neuroprotective [113,122] effects. This evidence suggests that bioactive peptides are encrypted in the protein native structure and are released during the hydrolysis process. Depending on the hydrolysis conditions (i.e., type of proteases used, period, and time of hydrolysis), hydrolysates with different kinds and efficiency degrees of activity can be obtained. This is due to the fact that hydrolysis conditions can influence the type of obtained peptides, namely the size and the amino acid profile—and hence, the structure—which in turn, influence the activity and the function of peptides. In this context, literature data agree that important factors which affect the bioactivities of the peptides are their molecular weight and amino acid composition. In general, low-molecular weight peptides are more bioactive than the high-molecular weight ones, since they more easily escape enzymatic degradation in the gastrointestinal tract, and therefore, they can be absorbed and introduced as such into the blood stream than larger peptides. Moreover, small peptides are likely more easily able to interact with specific target sites, such as an enzyme’s active site, in comparison to larger peptides. Instead, the peptide’s amino acid composition is fundamental to define its structure and, therefore, to influence the strength and the efficiency of the interaction with the peptide’s target site; in fact, the amino acids composition is the basis of the peptide’s structure-function relationship.
Hempseed oil unsaponifiable matter: tocopherol profile.
What is hemp?
Hemp is a variety of Cannabis sativa L. Hemp is a dioecious plant, which means that it can be separated into male and female plants. In hemp fields, there is usually a concentration of female hemp and sporadic placed males to pollinate the females and produce nutrient-rich seeds. Hemp has been used for over 10,000 years to make paper and fibres for clothing and fabric, but also in cosmetic products, particularly as an oil but also as other extracts and derivatives.
To this date, cosmetic regulatory compliance of CBD as an ingredient itself relies on the part of the plant from which it is extracted. For instance, seeds when not accompanied by tops are acceptable, although these do not contain CBD, whereas CBD prepared from Cannabis extracts or tinctures from flower/fruiting tops where the resin has not been separated, as well as the separated resin, are not allowed for use. Indeed, the UN 1961 Single Convention on Narcotic Drugs defines controlled cannabis as “the flowering or fruiting tops of the cannabis plant”, but does not consider Cannabis sativa seeds or leaves as controlled substances (as long as they are not accompanied by the tops).
Can cannabidiol (CBD) be used in cosmetics?
Cannabidiol (CBD) is a type of cannabinoid that can be synthetically produced or isolated from Cannabis plants and used as a single ingredient. In cosmetics, CBD can function as an antioxidant and facilitate anti-aging properties.