# Remedial Prospective ofHippophae rhamnoides Linn. (Sea Buckthorn)

Authors: Chirag A. Patel; Kalyani Divakar; Devdas Santani; Himanshu K. Solanki; Jalaram H. Thakkar
Journal: ISRN Pharmacology
 (2012)

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## Abstract

Sea buckthorn (Hippophae rhamnoides L.) constitutes thorny nitrogen fixing deciduous shrub. Sea buckthorn(SBT) is primarily valued for its very rich vitamins A, B1, B12, C, E, K, and P; flavonoids, lycopene, carotenoids, and phytosterols. and therapeutically important since it is rich with potent antioxidants.  Scientifically evaluated pharmacological actions of SBT are like inflammation inhibited by reduced permeability, loss of follicular aggregation of lymphocytes from the inflamed synovium and suppress lymphocyte proliferation. SBT-reduced recurrence of angina, ischemic electrocardiogram which might be due to decreased myocardial oxygen consumption and inhibition of platelet aggregation induced by collagen. SBT can kill both cancer cells of S180, P388, SGC7901 and lymphatic leukemia (L1200). The antiulcer activity may be related to reduce gastric empty time, inhibiting proteolytic activity and promoting wound reparation processes of mucosa. SBT exerts antihypertensive effect in part by blocking angiotensin-2 receptor on cell surface. SBT decreased the level of stress hormones and enhanced hypoxic tolerance in animals indicating its anti-stress, adaptogenic activity. A lot of research work is still needed to find cellular and molecular mechanisms of  these activities and also yet to be explored for its activity in osteoporosis, hemorrhage, cataract, urinary stone, acne, psoriasis, polyneuritis, cheilosis, glossities, baldness, anti-obesity, gout, and chronic prostitis.


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## Body

## 1. Introduction

Sea buckthorn (Hippophae rhamnoidesL., Elaeagnaceae) constitutes a thorny nitrogen fixing deciduous shrub which cultivated various parts of the world for its nutritional and medicinal values [1]. A Sea buckthorn fruits (Figure 1), seed (Figure 2) and other parts is primarily valued for its very rich vitamins A, B1, B12, C, E, K and P; flavonoids, lycopene, carotenoids,  and phytosterols. Therapeutically important because it is rich with potent antioxidants [2–4]. These compounds are of interest not only from the chemical point of view, but also because many of them possess biological and therapeutic activities including antioxidant, cardiovascular, cancer therapy, healing, anti-inflammation, antiradiation effect, treatment of gastrointestinal ulcers, as a liver protective agent, antioxidant, platelet aggregation, and immunomodulator [5]. Because of these effects, H. rhamnoidesL. containing bioactive compounds is often used in traditional medicine. See Table 1 for Constituents of Sea buckthorn Fruit.Table 1
Constituents of Sea buckthorn Fruit [2].
Sr. no.Constituents of sea buckthorn fruit   (Per 100 grams fresh berries)1The main unsaturated fatty acids are oleic acid (omega-9), palmitoleic acid (omega-7), palmitic acid and linoleic acid (omega-6), and linolenic acid (omega-3); there are also saturated oils and sterols (mainlyβ-sitosterol)6–11% (3–5% in fruit pulp, 8–18% in seed) fatty acid composition∖and total oil content vary with subspecies2Vitamin C28–310 mg (typical amount: 600 mg)3Carotenoids, including beta carotene, lycopene, and zeaxanthin; these contribute to the yellow-orange-red colors of the fruit32–45 mg fatty acids (oils)4Vitamin E (mixed tocopherols)Up to 180 mg (equal to about 270 IU)5Folic acidUp to 80 mcg6Organic acids for example, quinic acid, malic acid; ingredients similar to those are found in cranberriesQuantity not determined expressed juice has pH of 2.7–3.37Flavonoids (e.g., mainly isorhamnetin, quercetin glycosides, and kaempferol)50–500 mg (0.05% to 0.5%)Figure 1
Sea buckthorn fruits.Figure 2
Sea buckthorn seeds.


## 2. Manufacture of Sea Buckthorn Products

Figure3 is a diagram of a processing method that can be used to separate useful components of the berries, yielding the key products of juice, dried fruit nutrients, and oil from the seeds and pulp; residues can be utilized as valuable animal feed. New technologies, involving supercritical carbon dioxide extraction, are now being used in China to efficiently produce the oil products.Figure 3
Flow diagram of manufacturing of product from sea buckthorn.


## 3. Pharmacological Account of Sea Buckthorn with Recommendation Mechanism of Action

### 3.1. Platelet Aggregation

Cheng et al. suggest that total flavonoids ofH. rhamnoidesL. (TFH) may suppress platelet aggregation induced by collagen, probably due to the inhibition of tyrosine kinase activity. It has been reported that collagen receptor stimulation leads to tyrosine phosphorylation of Syk (Spleen tyrosine kinase) or Src (proto-oncogene encoding a tyrosine kinase), followed by phospholipase C-gamma 2 activation. Tyrosine kinase activation increases intracellular calcium and activates phospholipids A2 (PLA2), followed by synthesis of arachidonic acid from phospholipids in plasma membrane [5]. The rate of aggregation reaction (% aggregation/min) was also reduced by SBT supplementation [6].


### 3.2. Antioxidant and Antibacterial

The Sea buckthorn leaf extract exhibited inhibitory effect on the chromium-induced effect of plasma MDA levels. It also restored the intracellular antioxidants such as reduced glutathione (GSH) and Glutathione peroxidase (GPx) and also exhibited inhibition of ROS/free radical production [7, 8]. It also showed maintenance of mitochondrial and nuclear integrity as well as restoring the phagocytosis by macrophages [9]. The extract also protected animals significantly from the hepatotoxicity by decreasing creatine phosphokinase (CPK), serum glutamate oxaloacetate transferase (SGOT), and serum glutamate pyruvate transferase (SGPT) level compared to the chromium-treated animals [10].


### 3.3. Antiulcer

The antiulcer action of sea buckthorn oils related to an increased in the hydrophobicity of the mucosal surface, retarded the gastric emptying [11], inhibited lipid peroxidation in gastric mucosa, accelerated of the mucosal repair [12], inhibited proteolytic activity in gastric liquid, promoted the wound reparation processes of mucosa and prevent mucosa damage [13].


### 3.4. Anti-Inflammatory

Lymphocyte proliferation decreased by SBT clearly indicates inhibition of T-cell activation [14]. Due to the presence of some mitogens in SBT, it stimulated lymphocyte proliferation [15]. SBT had reductive effect on C-reactive protein, a marker of inflammation and a risk factor for cardiovascular diseases [16]. It was possible that inhibition of nitric oxide (NO) production by SBT leaf extract could be due to inhibition of transcription of the iNOS gene which was quite evident at translation level on probing with Moab against iNOS. The onset of the NO production cascade induced by lipopolysaccharides in macrophages required a number of steps such as the activation of nuclear factor (NF)-kh and subsequent iNOS mRNA expression [17].


### 3.5. Anticancer

H. rhamnoides L., with major constituents includes, quercetin-induced apoptosis in cancer cells, such as HT- 29 human colon cancer cells, HL-60, and K562 human leukemia cells, baicalin-induced apoptosis in prostate cancer cells. Sea buckthorn juice not only inhibits growth of the human gastric carcinoma (SGC7901) and lymphatic leukemia (L1200) but kills both S180 and P388 cancer cells [18]. SBT juice decreased genotoxic effect of cisplatin on somatic and germ cell of mice [19]. SBT fruit is able to decrease carcinogen-induced stomach and skin tumorigenesis, which might involve upregulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect [20]. SBT can be anticipated that the antimutagenic activity via antioxidative mechanism [21]. Sea buckthorn juice can block the endogenous formation of N-nitroso compounds more effectively than ascorbic acid and thereby prevent tumor production [22–24].


### 3.6. Hepatic Disease

Sea buckthorn could reduce the serum levels of laminin, hyaluronic acid, total bile acid (TBA), and collagen types III and IV in patients with liver cirrhosis, demonstrating that it may restrain the synthesis of collagen and other components of extracellular matrix [25]. SBT also fixes vitamin A and RAR contents of hepatic stellate cells (HSCs), so as to keep HSCs in a quiescent status and to prevent progression of liver fibrosis [26]. SBT has apparent hepatoprotective properties and alleviating liver injury caused by carbon tetrachloride [27].


### 3.7. Cardiac Effect

TFH could improve the mechanocardiography and the ischemic electrocardiogram. SBT increased the internal pressure peak of the left ventriculus and its maximum rate of change (dp/dtmax) distinctly, the time from the left ventricle starting a contraction to the occurrence of a dp/dtmax was shortened 4 distinctly, the diastolic pressure of the left ventricle and the left ventricular pressure of the isovolumetric relaxation phase diminished, and cardiac output, cardiac index, heart stroke index, and left ventricular power index of the myocardium increased [28]. Further research showed that TFH could strengthen the contractility of the extracorporeal papillary muscles of guinea pigs. TFH could prolong the time of ventricular fibrillation, postpone the atrioventricular conduction, lower the heart rate, and attenuate the myocardial contractility [29].


### 3.8. Antihypertensive Effect

In view of the previous researches that TFH is effective in decreasing the concentration of intracellular-free calcium induced by angiotensin-2 in vascular smooth muscle cells by blocking receptor-operated calcium channels, it is possible to conclude that TFH exerts its antihypertensive effect, in part, by blocking angiotensin-2 receptor on cell surface and thus arrest downstream signal pathway. In sum, hypertension, hyperinsulinemia, dyslipidemia, and activated angiotensin-2 provoked by the high-sucrose diet can be ameliorated or modulated by total flavones purified from seed residues ofHippophae rhamnoidesL., and the best effect was shown at the dose of 150 mg/kg/day [30].


### 3.9. Healing

SBT promotes cutaneous wound healing [31], burns wound healing [32], and dermals wound healing [33] by increasing antioxidant and protecting again sulfur dioxide [34] and mustard-gas-induced injury [35]. TFH enhanced mechanical strength of healing tendons and can thus be credited to enhance collagen deposition and collagen maturation with an altered cytokine profile in the wound. TFH may increase TGFβ1 and fibrogenic cytokine that stimulates collagen production in tendons and decreases COX-2 in the healing tendons [36, 37]. Sea buckthorn seed oil significantly attenuated hypoxia-induced oxidative stress, maintaind blood-brain barrier membrane integrity, restricted the rise in plasma catecholamine, and significantly enhanced the hypoxic tolerance in experimental animals [38]. SBT seed oil also decrease the level of stress hormones and enhances hypoxic tolerance in animals exposed to hypoxia indicating its antistress and adaptogenic activity against hypoxia [39].


### 3.10. Radiation

The radio protective effect generated by SBT at molecular level in terms of free radical scavenging as studied through in-vitro studies could explain the cellular survival, proliferation enhancement, immunostimulation, and ultimately the whole body survival [40]. Maintenance of chromatin organization, induction of hypoxia, protects hydrogen atom donation, free radical scavenging [41], and blocking of cell cycle at G2-M phase by interfering with topoisomerase-I activity and mitochondrial and genomic DNA from radiation seem to contribute towards the radio protective efficacy of SBT [42].


### 3.11. Atopic Dermatitis

Sea buckthorn seed oil treatment increased the level of a-linolenic, linoleic, and eicosapentaenoic acids, whereas pulp oil supplementationβ-Sitosterol and β-carotene in the oils may also have effected on the symptoms of Atopic dermatitis [43].


### 3.12. Anti-Atherogenic and Hypoglycemic Activity

Atherogenic index (AI) was significantly reduced and acetylcholine-induced vasorelaxation was markedly impaired which could be restored to control values in SBT seed oil treated normally and hypercholesterolemic animals [44]. SBT decreases blood glucose and lipid in normal mice, and effect of SBT on glycometabolism may be related to the control of gluconeogenesis [45].


## 3.1. Platelet Aggregation

Cheng et al. suggest that total flavonoids ofH. rhamnoidesL. (TFH) may suppress platelet aggregation induced by collagen, probably due to the inhibition of tyrosine kinase activity. It has been reported that collagen receptor stimulation leads to tyrosine phosphorylation of Syk (Spleen tyrosine kinase) or Src (proto-oncogene encoding a tyrosine kinase), followed by phospholipase C-gamma 2 activation. Tyrosine kinase activation increases intracellular calcium and activates phospholipids A2 (PLA2), followed by synthesis of arachidonic acid from phospholipids in plasma membrane [5]. The rate of aggregation reaction (% aggregation/min) was also reduced by SBT supplementation [6].


## 3.2. Antioxidant and Antibacterial

The Sea buckthorn leaf extract exhibited inhibitory effect on the chromium-induced effect of plasma MDA levels. It also restored the intracellular antioxidants such as reduced glutathione (GSH) and Glutathione peroxidase (GPx) and also exhibited inhibition of ROS/free radical production [7, 8]. It also showed maintenance of mitochondrial and nuclear integrity as well as restoring the phagocytosis by macrophages [9]. The extract also protected animals significantly from the hepatotoxicity by decreasing creatine phosphokinase (CPK), serum glutamate oxaloacetate transferase (SGOT), and serum glutamate pyruvate transferase (SGPT) level compared to the chromium-treated animals [10].


## 3.3. Antiulcer

The antiulcer action of sea buckthorn oils related to an increased in the hydrophobicity of the mucosal surface, retarded the gastric emptying [11], inhibited lipid peroxidation in gastric mucosa, accelerated of the mucosal repair [12], inhibited proteolytic activity in gastric liquid, promoted the wound reparation processes of mucosa and prevent mucosa damage [13].


## 3.4. Anti-Inflammatory

Lymphocyte proliferation decreased by SBT clearly indicates inhibition of T-cell activation [14]. Due to the presence of some mitogens in SBT, it stimulated lymphocyte proliferation [15]. SBT had reductive effect on C-reactive protein, a marker of inflammation and a risk factor for cardiovascular diseases [16]. It was possible that inhibition of nitric oxide (NO) production by SBT leaf extract could be due to inhibition of transcription of the iNOS gene which was quite evident at translation level on probing with Moab against iNOS. The onset of the NO production cascade induced by lipopolysaccharides in macrophages required a number of steps such as the activation of nuclear factor (NF)-kh and subsequent iNOS mRNA expression [17].


## 3.5. Anticancer

H. rhamnoides L., with major constituents includes, quercetin-induced apoptosis in cancer cells, such as HT- 29 human colon cancer cells, HL-60, and K562 human leukemia cells, baicalin-induced apoptosis in prostate cancer cells. Sea buckthorn juice not only inhibits growth of the human gastric carcinoma (SGC7901) and lymphatic leukemia (L1200) but kills both S180 and P388 cancer cells [18]. SBT juice decreased genotoxic effect of cisplatin on somatic and germ cell of mice [19]. SBT fruit is able to decrease carcinogen-induced stomach and skin tumorigenesis, which might involve upregulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect [20]. SBT can be anticipated that the antimutagenic activity via antioxidative mechanism [21]. Sea buckthorn juice can block the endogenous formation of N-nitroso compounds more effectively than ascorbic acid and thereby prevent tumor production [22–24].


## 3.6. Hepatic Disease

Sea buckthorn could reduce the serum levels of laminin, hyaluronic acid, total bile acid (TBA), and collagen types III and IV in patients with liver cirrhosis, demonstrating that it may restrain the synthesis of collagen and other components of extracellular matrix [25]. SBT also fixes vitamin A and RAR contents of hepatic stellate cells (HSCs), so as to keep HSCs in a quiescent status and to prevent progression of liver fibrosis [26]. SBT has apparent hepatoprotective properties and alleviating liver injury caused by carbon tetrachloride [27].


## 3.7. Cardiac Effect

TFH could improve the mechanocardiography and the ischemic electrocardiogram. SBT increased the internal pressure peak of the left ventriculus and its maximum rate of change (dp/dtmax) distinctly, the time from the left ventricle starting a contraction to the occurrence of a dp/dtmax was shortened 4 distinctly, the diastolic pressure of the left ventricle and the left ventricular pressure of the isovolumetric relaxation phase diminished, and cardiac output, cardiac index, heart stroke index, and left ventricular power index of the myocardium increased [28]. Further research showed that TFH could strengthen the contractility of the extracorporeal papillary muscles of guinea pigs. TFH could prolong the time of ventricular fibrillation, postpone the atrioventricular conduction, lower the heart rate, and attenuate the myocardial contractility [29].


## 3.8. Antihypertensive Effect

In view of the previous researches that TFH is effective in decreasing the concentration of intracellular-free calcium induced by angiotensin-2 in vascular smooth muscle cells by blocking receptor-operated calcium channels, it is possible to conclude that TFH exerts its antihypertensive effect, in part, by blocking angiotensin-2 receptor on cell surface and thus arrest downstream signal pathway. In sum, hypertension, hyperinsulinemia, dyslipidemia, and activated angiotensin-2 provoked by the high-sucrose diet can be ameliorated or modulated by total flavones purified from seed residues ofHippophae rhamnoidesL., and the best effect was shown at the dose of 150 mg/kg/day [30].


## 3.9. Healing

SBT promotes cutaneous wound healing [31], burns wound healing [32], and dermals wound healing [33] by increasing antioxidant and protecting again sulfur dioxide [34] and mustard-gas-induced injury [35]. TFH enhanced mechanical strength of healing tendons and can thus be credited to enhance collagen deposition and collagen maturation with an altered cytokine profile in the wound. TFH may increase TGFβ1 and fibrogenic cytokine that stimulates collagen production in tendons and decreases COX-2 in the healing tendons [36, 37]. Sea buckthorn seed oil significantly attenuated hypoxia-induced oxidative stress, maintaind blood-brain barrier membrane integrity, restricted the rise in plasma catecholamine, and significantly enhanced the hypoxic tolerance in experimental animals [38]. SBT seed oil also decrease the level of stress hormones and enhances hypoxic tolerance in animals exposed to hypoxia indicating its antistress and adaptogenic activity against hypoxia [39].


## 3.10. Radiation

The radio protective effect generated by SBT at molecular level in terms of free radical scavenging as studied through in-vitro studies could explain the cellular survival, proliferation enhancement, immunostimulation, and ultimately the whole body survival [40]. Maintenance of chromatin organization, induction of hypoxia, protects hydrogen atom donation, free radical scavenging [41], and blocking of cell cycle at G2-M phase by interfering with topoisomerase-I activity and mitochondrial and genomic DNA from radiation seem to contribute towards the radio protective efficacy of SBT [42].


## 3.11. Atopic Dermatitis

Sea buckthorn seed oil treatment increased the level of a-linolenic, linoleic, and eicosapentaenoic acids, whereas pulp oil supplementationβ-Sitosterol and β-carotene in the oils may also have effected on the symptoms of Atopic dermatitis [43].


## 3.12. Anti-Atherogenic and Hypoglycemic Activity

Atherogenic index (AI) was significantly reduced and acetylcholine-induced vasorelaxation was markedly impaired which could be restored to control values in SBT seed oil treated normally and hypercholesterolemic animals [44]. SBT decreases blood glucose and lipid in normal mice, and effect of SBT on glycometabolism may be related to the control of gluconeogenesis [45].


## 4. Pharmacological Effects of Sea Buckthorn yet to Be Explored in Relation with Other Diseases

SBT is a traditional herbal medicine, which has long used many condition like relieving cough, diarrhea, aiding digestion, invigorating blood circulation alleviating pain, treating colitis and enterocolitis since ancient time because it is rich of antioxidant. Juice, syrup, and oil of the fruits have been used in disantheria, osteoporosis, hemorrhage, cataract, urinary stone, acne, psoriasis, sterility, polyneuritis, cheilosis, glossitis, baldness, analgesic, benign prostatic hypertrophy, antiobesity, gout, and chronic prostitisas a metabolism regulator in traditional medicine [46].


## 5. Sea Buckthorn Market Products [47]

See Table2.Table 2
List of available sea buckthorn market products.
Product nameManufacturer nameSea buckthorn oil softgelFraken biochem co., ltd. [Shandong, China]Fructus hippophae extractRui heng industry co., ltd. [China]Sea buckthorn pulp oilInner mongolia yuhangren hi-tech industrial co., ltd. [province: Inner Mongolia, China]Sea buckthorn seed oilHebei shenxing sea buckthorn health products co., ltd. [China]Immune-enhancing ingredientsShanghai brightol international co., ltd. [province:shanghai, China]Fish oil softgel capsule & lecithin softgel capsuleQingdao dacon trading co., ltd. [province:Shandong, China]Sea buckthorn berry oil sea buckthorn seedsBeijing powdery food co., ltd. [province:Beijing, China]Oil capsule (y-o-04)Youchain group co., ltd. [province:Hebei, China]Shenxing sea buckthorn xinzhian oral liquidHebei shenxing sea buckthorn health products co., ltd. [province:Hebei, China]Organic sea buckthorn fruit oil soft capsuleHebei shenxing sea buckthorn health products co., ltd. [province:Hebei, China]Organic sea buckthorn berry/fruit powderHebei shenxing sea buckthorn pharmaceutical co., ltd. [province:Hebei, China]Sea buckthorn fruit oil capsules-1Jinan sea buckthorn trade co., ltd. [province:Shandong, China]Jinan sea buckthorn trade co., ltd. [province: Shandong, China]Jinan sea buckthorn trade co., ltd. [province:Shandong, China]Seabuckthorm seed oil capsuleWutai mountain sea buckthorn co., ltd. [province:Shanxi, China]Sea buckthorn berry powderShijiazhuang yiling pharmaceutical co., ltd. [province:Beijing, China]Sea buckthorn powderBeijing powdery food co., ltd. [province:Beijing, China]SpirulinaDechen nutrachem co., ltd. [province:Shandong, China]Sea buckthorn seed oil (flu-s003)Inner mongolia prosperous earth trade co., ltd. [province:Inner Mongolia, China]Sea buckthorn seed oil (flu-s004)Inner mongolia prosperous earth trade co., ltd. [province:Inner Mongolia, China]Sea buckthorn oilGuangzhou honsea sunshine bio science & technology co., ltd. [province:Guangdong, China]Sea buckthorn seed oil capsule (hy-08003)Beijing huiyuan group youyu co., ltd. [province:Shanxi, China]Sea buckthorn galic softgel (psg)Perfect (China) co., ltd. [province:Guangdong, China]Sea buckthorn fruit oilWutai mountain sea buckthorn co., ltd. [province:Shanxi, China]Fruit juice concentrateHeilongjiang provincial hongri trading co., ltd. [province:Heilongjiang, China]Sea buckthorn effervescent tabletsNanjing union biotech co., ltd. [province:Jiangsu, China]Frozen sea buckthorn berryConseco sea buckthorn co., ltd. [province:Beijing, China]Digestive support herbal candyCandy manufacturer inc. [province:Guangdong, China]Capsules of nutrient productsShanghai honghao chemicals co. Ltd. [province:Shanghai, China]Menova heyeqianzi slimming herbs capsulepanda international trade co., limited [province:Hong Kong, China]Softgel capsule[2010-08-17]Sunrise nutrachem group [province:Shandong, China]Skin whitening productChifeng wedge pharmaceutical co., ltd. [province:Inner Mongolia, China]


## 6. Conclusion

SBT has high-nutritional and medicinal values due to its very rich antioxidant property. It is a widely used plant in traditional medicine for various clinical conditions. Scientifically evaluated pharmacological effects of it are like antiulcerogenic effect, in vitro and in vivo antioxidant effects, cardiac disease, antiatherogenic effect, radio protective effects, beneficial effects on experimental injury and clinical diseases of the liver, nad inhibition of platelet aggregation. Lot of research work is still needed to find cellular and molecular mechanisms of these activities.



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*Source: 436857-2012-03-11.xml*