Sea Buckthorn

Sea Buckthorn (Hippophae rhamnoides of the family Elaeagnaceae) is a small shrub (3-15 feet in height) that is known to grow in high altitudes of 7,000-15,000m above sea level in the north west Himalaya region.^[1] Its berries are sometimes drunk as either a juice or wine^[2] and can also be used for producing oils.^[3] Both the berries and the leaves can be used as dietary supplements.

It is a Traditional Chinese Medicine mentioned in the Sibu Yidian (Tang Dynasty) and Jing Zhu Ben Cao (Qing Dynasty) and was first mentioned in the Chinese Pharmacopoeia in 1977.^[4]

Sea Buckthorn contains:

• Hippophaeosides A-C^[5]
• Hippophins C-F (seeds of the sinensis variant^[6]) which are kaempferol glycosides

There are some molecules that are (currently known to be) unique to sea buckthorn and are named after it accordingly. They appear to be flavonoid glycosides

• Procyanidins^[7] comprised of catechin, epicatechin, gallocatechin, and epigallocatechin^[8]
• Various forms of Quercetin (itself at 29.7µg/g in the seeds only) including Pentamethylquercetin,^[9] Isorhamnetin (3.74-147µg/g and highest in leaves^[10] or 27.91-112.65µg/g in water extracts^[11]) and related glycosides,^[12][13] Quercetin-3,O-galactoside (34.98-334µg/g and highest in leaves),^[10] Quercetin-3-O-glucoside-7-O-rhamnoside,^[13] and Rutin (155-365µg/g and highest in leaves)^[10]
• Myricetin (27.1-161.7µg/g)^[10]
• Kaempferol (4.29-54.6µg/g^[10][14] or 10.74-46.43µg/g^[11]) and glycosides^[6][15]
• Tiliroside (0.05%)^[5]
• Zeaxanthin as the most abundant carotenoid^[16] at 2.34-3.34mg/g^[17][16] and a particular abundance of the Zeaxanthin-C16:0,C16:0 ester (18.53-21.27% total carotenoids)^[16]
• Other carotenoids including neoxanthin (0.01-0.08% total carotenoids),^[16] Lutein (0.23-0.27% total carotenoids),^[16] β-carotene (14.68-29.06% total carotenoids),^[16] and γ-carotene (2.39-3.99% total carotenoids).^[16] Total carotenoids in the fruits range from 8.85-25.51mg/100g with an outlier of 43.06mg/100g^[18]
• Inositol^[19]
• Ursolic acid and ursolic aldehyde^[5]
• Methyl gallate and gallic acid^[5] and larger tannin structures such as casuarinin (leaves)^[20]
• Pomolic acid^[5]
• Panthenoic Acid (Vitamin B5) in the berries^[21]
• Vitamins B1, B2, and B6 in the berries^[21]
• Nicotinamide, Folate, and Biotin in the berries^[21][22]
• Vitamin C in the berries (0.4% or 400mg/100g by dry weight^[23])^[21]
• Vitamin E in the berries^[21]
• β-sitosterol^[5]

Beyond the hippophins, sea buckthorn appears to have a large variety of the standard polyphenolics with more relevant concentrations of quercetin and its analogues (isorhamnetin, quercetin glycosides) as well as procyanidins made of catechins. Kaempferol is also a large component, as it is also the backbone for the hippophins

The fatty acid composition (found in seed and berry oils with fat content, but not in supplements derived from leaves) includes:

• 23.4% (range of 17-27%) of palmitic acid^[24][25]
• 17.3% (range of 10-22%) of palmitoleic acid^[24][25]
• 1.5% of stearic acid^[24]
• 20.5%^[24] or 20-40% as a range of oleic acid^[25]
• 5.5% of vaccenic acid (18:1n7)^[24]
• 17.9% (10-20% range) of linoleic acid^[24][25]
• 11.4% of alpha-linolenic acid^[24]

Whereas volatile compounds include:

• Vomifoliol^[5]
• 2-methylbutanoic acid ethyl ester^[26]
• 3-methylbutanoic acid ethyl ester^[26]
• Hexanoic and octanoic acid ethyl esters^[26]
• 3-methylbutyl 2-methylbutanoate and 3-methylbutyl 3-methylbutanoate^[26]
• Benzoic acid methyl ester^[26]

The aforementioned compounds confer taste and aromatic properties to sea buckthorn, but their contributions to health effects are not known

The total antioxidant capacity of the plant appears to be about 0.2–18.2% (ABTS method) or 0.7–28.2% (TEAC method) as potent as Trolox (water soluble Vitamin E) using a variety of analytical methods, with the higher values thought to be more reflective of the plant as compounds could have been destroyed with other testing methods.^[10] Other studies have noted that gallic acid equivalents (GAE) of seabuckthorn are 76.07–93.72mg/g in the leaves^[11] (higher at 363mg/g in the water extract^[1]) and that seabuckthorn is less potent than Vitamin C in vitro.^[11] Total carotenoids can vary from 1.5−18.5mg/100g fresh weight of the berries.^[27]

Most antioxidants appear to accumulate in the seeds relative to the pulp, leaves, or stem, despite most flavonoids being in the leaves (and least in seeds).^[10] The total phenolic content of the leaves is 47.06–66.03mg/g rutin equivalents (RE).^[11]

The antioxidative potency of sea buckthorn is present and somewhat respectable, but when compared to the research standards (Vitamin E, Vitamin C, Gallic Acid) it appears to be significantly weaker

The main flavonoids of sea buckthorn (isorhamnetin, kaempferol and quercetin) appear to be absorbed following oral ingestion^[28] and solid dispersions of the flavonoids appear to have greater bioavailability than do the basic flavonoids or self-emulsifying delivery systems.^[29]

Isolated procyanidins from sea buckthorn appear to reduce the rate of protein absorption with an EC₅₀ somewhere between 39.8-65.8μg/mL, and the tested extracts were able to inhibit protein digestive enzymes in vitro with a potency of 57.5-67.7% (trypsin) and 44.1-60.3% (pepsin).^[30]

May possibly reduce the rate of protein absorption secondary to inhibiting enzymes of protein hydrolysis

Ingestion of sea buckthorn berries and extracts has been noted to delay the spike in triglycerides following a test meal in humans, although the total AUC of triglycerides (indicative of absorption) was unaffected.^[31] This was mostly attributed to the fiber component^[31] and is similar to previous literature looking at the influence of sea buckthorn berries on postprandial glycemia (carbohydrate absorption).^[32]

One rat intervention using 500-1,000mg/kg of the ethanolic extract of sea buckthorn noted reduced food intake in a dose-dependent manner and a decrease in leptin,^[4] whereas a study in children (with dyspepsia) has noted an increase in leptin and neuropeptide Y, suggesting an increase in appetite.^[33]

Unclear influences on appetite regulation

50-200mg/kg of sea buckthorn (75% ethanolic extract of leaves) for 21 days prior to scopolamine administration was able to dose-dependently reduce lipid peroxidation as assessed by MDA concentrations and acetylcholinesterase activity, both of which were fully normalized at 200mg/kg. Cognition also appeared to be preserved with sea buckthorn ingestion.^[34]

Oral sea buckthorn appears to have neuroprotective properties, and they are of moderate to respectable potency according to the preliminary evidence

A single dose of the water extract of sea buckthorn leaves appears to have adaptogenic properties in rats given a cold/hypoxia/restraint test, with the dosage of 100mg/kg taken 30 minutes prior having the most adaptogenic effect (recovery hastened by 42%) and 12.5mg/kg having some efficacy.^[1] Five days of dosing failed to outperform a single dose^[1] and the mechanisms are thought to be related to attenuating a shift to glycolytic metabolism during stress testing (or at least a preservation of glycogen).^[35][36]

Isolated isorhamnetin has been noted to inhibit apoptosis in cardiac cells via antioxidant effects (which eventually inhibited ERK activation)^[37] and 5-20mL/kg of the oil for 28 days prior to isoproterenol administration has been noted to reduce cardiac damage at the highest dose in rats.^[38]

Clotting time appears to be increased with sea buckthorn, with an infusion of 300mcg/kg of the flavones administered to mice prolonging clotting time by 36.7%.^[39] In vitro, a concentration of 3mcg/mL appears to be effective in reducing collagen-induced platelet aggregation.^[39]

The berry oil (made from seeds and berries) has been noted to reduce ADP-induced aggregation rate (3%) and maximal platelet aggregation (5-15% depending on concentration of ADP) when taken at the dosage of 5,000mg daily over the course of 4-8 weeks, relative to the active control of coconut oil.^[24]

Sea buckthorn has been shown to exert protection against hypoxia-induced vascular leakage.^[40] In rats subject to experimental polycythemia (an increase in blood volume and erythrocytosis associated with higher altitudes,^[41][42]) 35-140mg/kg of the flavonoids from sea buckthorn daily for five weeks is able to attenuate adverse changes with 70-140mg/kg being equally effective (and 35mg/kg being barely effective).^[43] This has been noted previously with isolated quercetin as two of its sources, buckthorn and ginkgo biloba, are sources of it and are used for high altitude sickness.^[44]

It has been noted that pentamethylquercetin is able to induce adiponectin expression (1-10μM but not 0.1-0.3μM) in differentiated adipocytes (without inherently affecting lipid accumulation) which appeared to be in part due to the observed upregulation of PPARγ mRNA^[45] and also thought to be partly due to reducing the effects of TNF-α and IL-6 (negative regulators of adiponectin^[46][47]) via reducing their secretion.^[45] That being said, elsewhere PPARγ is reduced by isorhamnetin which contributes to a suppression of adipogenesis and suppression of adiponectin secretion.^[48]

The overall methanolic extract has been noted to inhibit adipocyte triglyceride accumulation (35% at 30µg/mL), although the chloroform extract was more effective at 82%.^[5] The bioactive molecules underlying these effects were thought to be the triterpenoids (including ursolic acid) and flavonoid aglycones.^[5]

When an ethanolic extract of sea buckthorn (1,000mg/kg) is given to rats, hepatic expression of PPARγ appears to be increased.^[4]

Different isolated components in sea buckthorn seem to differentially modulate adipocyte function and growth. Overall, there is perhaps an increase in PPARγ

Supplementing mice with a 70% ethanolic extract of sea buckthorn at 500-1,000mg/kg bodyweight over 13 weeks was associated with reduced weight and fat gain when participants were subjected to an obesogenic diet. The sea buckthorn intervention was associated with a reduction in food intake, leptin concentrations in serum, and hepatic triglycerides.^[4]

This study noted that the 1,000mg/kg group had 47% lower liver fat than did normal diet control, despite being subject to a high fat diet (with the high fat diet control experiencing a 46% increase in dietary fat relative to control).^[4]

The 80% methanolic extract of sea buckthorn has been found to inhibit nitric oxide production in macrophages with 63% potency at a concentration of 30µg/mL.^[5] When testing isolated compounds with potency, it was found that possible explanatory molecules may be kaempferol (IC₅₀ of 18.2µM), quercetin (20.6µM), ursolic acid (17.8µM), 23-hydroxy ursolic acid (12.5µM), and pomolic acid (16µM).^[5]

In another study, TNF-α and IL-6 secretion from adipocytes has been noted to be reduced in vitro at 3-10μM (isolated pentamethylquercetin).^[45]

In persons on hemodialysis, 2,000mg of sea buckthorn daily for 8 weeks failed to significantly modify biomarkers of inflammation such as C-reactive protein and leukocyte count.^[49]

One study conducted in persons on renal dialysis using 2,000mg of sea buckthorn daily for 8 weeks failed to find a significant modification in the amount of oxidative DNA damage observed.^[49]

Sea buckthorn appears to have antiulcer properties, secondary to both its antioxidant properties^[7] and an ability to increase the hydrophobicity of the stomach and slow gastric emptying^[50] which occurs in a dose-depedent manner at 3.5-7mL/kg of the seed oil or extracts of the oil.^[7][50]

Some antiulcer properties have been noted in horses (against glandular ulcers but not nonglandular)^[51] and against acetic acid^[7][50] and stress-induced^[50] gastric ulcerations in rats.

The seed oil, composed of mostly procyanidins and the polyphenols, appears to have biologically relevant anti-ulcer properties in research animals. This has not been tested in humans.

Sea buckthorn water extract is able to prevent hepatocytes from oxidative cell death induced by hypoxia (causes increased reactive oxygen species and enzyme leakage indicative of membrane damage^[52][53]) with efficacy at 10µg/mL and near complete efficacy at 50µg/mL.^[14]

In the liver, oral ingestion of sea buckthorn (as wine) in mice subject to a high cholesterol diet and oxidative stress resulted decreased lipid peroxidation in the liver and a better lipid profile in serum.^[2]

Sea buckthorn oil at 2g daily appears to reduce symptoms of dry eye in humans.^[54][55] This appears to be associated with reducing the tear film hyperosmolarity^[54] (involved in the pathology of dry eyes as it activates inflammatory signalling^[56][57]) but not associated with altering the fatty acid composition of eye tissue.^[55]

Oral supplementation of a sea buckthorn extract (50mg/kg) daily for six weeks in irradiated nude mice is able to effectively prevent UV-induced changes in skin quality and wrinkling.^[58]

Appears to be protective of the skin following oral ingestion

Sea buckthorn appears to be a traditional remedy for increasing wound healing rates.^[59]

Oral ingestion of the oil from sea buckthorn (2.5mL/kg to rats) as well as topical application (200µL) are both effective in increasing the rate of healing in a burn model,^[60] and topical application of the isolated flavonoids (1% of solution) has been found to accelerate the healing of incision wounds.^[61] The healing properties appear to be associated with increased angiogenesis (as assessed by increased metalloproteinases 2 and 9 as well as VEGF expression).^[60][59]

Oral ingestion, as well as topical administration, show some efficacy in accelerating wound healing rates. There is currently no human evidence nor are there comparisons to reference drugs in order to assess potency

Acute toxicity studies suggest that the LD₅₀ value for the leaf water extract is greater than 10,000mg/kg bodyweight in rats when taken daily for 14 days^[1] and subchronic intake suggested that intakes of 1,000-2,000mg/kg for 14 days were associated with nontoxic changes in hepatic and renal weight.^[1]

One case study has noted that overconsumption of sea buckthorn has resulted in a yellowing of the skin over six months.^[62]