Progress of the components and biological activities of Morinda officinalis How

The Morinda officinalis How is “one of the top four south authentic traditional Chinese medicines”, widely distributed in South District of China, such as Fujian, Guangdong, Guangxi, Hainan, etc. Its roots are widely used for the treatment of sexual impotence, spermatorrhea, irregular menstruation, and female infertility in clinical. Many kinds of compounds (iridoid glycosides, anthraquinones, saccharides, organic acids, volatile oils and homogeneous polysaccharides) have been isolated from its roots and the relevant biological activities (pain-killing, antioxidant, antibacterial, anticancer, anti-inflammatory, anti-tubercular and cardiovascular action) were also studied. This review briefly describes the botanical description, plant taxonomy, history of medicinal development and the progress of the chemical components and biological activities of M. officinalis to provide a reference for the researchers. *Correspondence to: Jianping Yong, Xiamen Institute of Rare-earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, 361021, China, Tel: +86591-631-731-62; E-mail: jpyong@fjirsm.ac.cn Canzhong Lu, Fujian Institute of Research on the Structure of Matter, Haixi Institute, Chinese Academy of Sciences, Fuzhou, 350002, China, Tel: +86-59183705794; E-mail: czlu@fjirsm.ac.cn


Introduction
Over the years, plant medicines have been used as helpful sources for curing different ailments both for human and animals [1][2][3]. Plant medicines contain a large variety of constitutes which have important protective and medicinal therapies [4][5][6][7]. Products from plant medicines have ever been widely used in Asia and Africa [3,7].
In Asia and Africa, almost all the population depend on traditional health doctors, thereby medicinal plants are used to meet health needs [1,3,7]. Modern medicines exist alongside with traditional herbal medicines still keep up their reputation for the cultural and historical reasons. Herbal products are widely accessible commercially, particularly in developed countries. In developed countries, the herbal medicines are greatly used to cure different ailments [7,8]. The assessment of different herbal products based on their uses and therapeutic value lead to the detection of novel medicines for curing various diseases.
M. officinalis is one kind of subtropical and tropical plants, which widely distribute in subtropical and tropical districts of Asia [9,10]. The root of this plant is well known as "Bajitian" in China, which has been used for curing various diseases in clinical.
This review briefly describes the botanical description, plant taxonomy, history of medicinal development and the progress of the components and biological activities of M. officinalis to provide a reference for the researchers.

Distribution and botanical description
M. officinalis mainly found in the upland tropical and subtropical forests of Asia. In China, it is widely distributed in south districts such as Fujian, Guangdong, Guangxi, Hainan, etc. [11]. Its branches covered with a small leaf-like appendage. Root succulent hypertrophy, irregular, cylindrical, and intermittent swelling with a rosary. The young M. officinalis plant is with stiff, slender bristles and covered with fine soft hairs; it gradually becomes hairless with rough surface and the branches covered with a small leaf-like appendage at maturity. M. officinalis flowers are arranged in fascicules and in umbels, and thickly hairy change to slender bristles showing its ageing stage; the flower is merged for half receptacle; the calyx is pubescent to smooth; the corolla is white, bell-shaped or urn inside, and hairy, finely hirsute outside; the aggregate fruits is orbicular to flatten; and the fruits are fully fused, red and subglobose [12].

History of medicinal development
The dried root of M. officinalis is a renowned traditional Chinese medicine and was listed in the Chinese Pharmacopoeia [15]. The roots have been used dated back to the late Qing Dynasty, Qingyuan, Sankeng and Luoding of Guangdong province, considered as one of the most important medicinal herbs (According to "Yaowu Chuchanbian" book, before Qing Dynasty medicinal materials used was Damnacanthus officinarum Huang (Rubiaceae) and Schisandra propinqua (Wall.) Hook.f. et Thoms. var. sinensis Oliv (Magnoliaceae).
M. officinalis can also be named locally as Jichang feng, Tuzi chang, Tuer chang, Heiteng zhuan, Maochang jin, and Jiyan teng. Root of M. officinalis is sharp, sweet and non-toxic, which can diffuse directly to the liver and kidney regions. This plant is well known to be medicinal to internal organs, such as the heart, the liver and the kidney, with other beneficial effects to man's health by nourishing kidney, strengthening bones, muscles and improving the circulation blood. M. officinalis root is extensively used in traditional Chinese medicine for curing diseases associated with kidney-yang deficiency: including fatigue, declining libido, premature ejaculation, male impotence, female infertility, rheumatism, muscular and skeletal atrophy and depression. The root of this plant has been accepted by the Health and Family Planning Commission of China for curing different ailments and can also be combined with other herbals to increase its treatment scopes.
Almost all parts of M. officinalis have been supported and approved by the Health and Family Planning Commission of China for treating different diseases in clinical, which include poor digestion, respiratory problems, immune deficiencies and high blood pressure in China since ancient times [15,[17][18][19][20][21][22].

Anti-inflammatory activity
The root of M. officinalis was reported to contain monotropeins, which exhibited higher anti-inflammatory and antinociceptive activities. It has been reported that the monotropein isolated from the root of M. officinalis can lengthen the action time, decrease stretching episodes, writhing antinociceptive assays and significantly diseased acute paw edema at the dosage of 20 and 30 mg/kg [25]. The literature also reported that the methanol extraction of M. officinalis root possess the antinociceptive and anti-inflammatory effects in-vitro and in-vivo by restraining inducible Nitric Oxide Synthase (iNOS), Cyclo-oxygenase (COX-2) and Tumour Necrosis factor-alpha (TNF-α) expression by down-regulating the NF-κB (Nuclear factor kappa-lightchain-enhancer of activated B cell) [26].The evidence also suggested that the Monotropein isolated from the roots of M. officinalis can decrease the ailment activity index; it also exhibited antimicrobial activity and inflammation by restraining NF-κB activation in colon mucosa [32]. Monotropein effectively inhibited mRNA expression of Cyclo-oxygenase (COX-2), Nitric Oxide Synthase (iNOS), Tumour Necrosis factor-alpha (TNF-α) and IL-1β in LPS-induced RAW 264.7 macrophages [33]. Liang et al. reported that the extractions of M. officinalis root can affect the chronic colitis and T lymphocytes in mice model by reducing the symptoms of ulcerative colitis and decreasing inflammatory cytokine levels [34].

Antioxidant activities
Gao reported that the polysaccharides from M. officinalis can reduce the Malondialdehyde (MDA) levels in liver of mice at every dosage. The result showed that he MDA levels were significantly lower in every dosage groups than those in the control and Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px). While the reduced Glutathione (GSH) activities were significantly higher in every dosage groups than those in control groups [35].
Similarly, aqueous extracts of M. officinalis can also enhance the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), which decrease the amount of Malondialdehyde (MDA) in the muscle tissue, liver tissue and blood of the forced swimming test mice [36]. The aqueous extracts of M. officinalis can enhanced the activity of Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-Px), Calcium ATPase (PMCA) and Na+/K+-ATPase of the major muscles of the forced swimming test mice, and enhanced the antioxidant activity of major muscles in the rats [37].
Mengyong et al. [38] reported that the polysaccharides from M. officinalis can increase the antioxidant enzyme activities and decrease in MDA levels of the testing rats. Acidic polysaccharides of M. officinalis possessed excellent free radical scavenging activity, which was suggested to be helpful to exhaustive exercise-induced oxidative stress [39].
Soon and Tan reported that extract of M. officinalis decreased the fasting blood glucose, hepatic and renal Thiobarbituric Acid Reactive Substances (TBARS) level and significantly improved the hepatic Superoxide Dismutase (SOD), Catalase (CAT) activities as well as Glutathione (GSH) levels in streptozotocin-induced diabetic rats [40].
It reported that M. officinalis can scavenge the superoxide anion and hydroxyl radicals in the chemiluminescence reaction of luminal-H 2 O 2 -CuSO 4 system [41]. The extract of M. officinalis was also found to scavenge the 2,2-dipicrylhydrazyl radicalin TM 3 cells, which showed no effect on cytotoxicity [27].

Antidepressant activity
It has reported that M. officinalis root possessed anti-anxiety and antidepressant properties [18,40]. Cui et al. [42] also reported that some compounds from the roots of Morinda officinalis How M. officinalis possess antidepressant activity. Li et al. [43] reported that Inulin-type Hexasaccharide (IHS) can protect the PC12 cell lines at the concentrations of 0.625, 1.25 µM from the lesion-induced-Corticostrone, while desipramine can protect the PC12 cell lines at the concentrations of0.25, 1µM. Qiu et al. reported that the aqueous extract of M. officinalis possess antidepressant activity. The result showed that the aqueous extract of M. officinalis can significantly improve reinforcement rate in the schedule of reinforcement at 72-seconds in mice and a significant decrease in the period of immobility. But this extract did not show good effect on spontaneous motor activity [44]. It was also reported that the aqueous extracts M. officinalis can improve the period of swimming loaded mice and regulate the level of monoamine neurotransmitters and reduce the level of 5-Hydroxytrytophan in the tissue of brain by balancing `the levels of noradrenaline, dopamine and epinephrine in brain [10].
It was also reported that the ethanol extract of M. officinalis possess antidepressant property in the mice and rats in forced swimming test model, while the aqueous extract exhibited antidepressant activity in male mice in forced swimming test model [45][46].

Anti-fatigue activity
Polysaccharides of M. officinalis were found to possessed antifatigue activity, when tested in loaded swimming model mice at 50, 100 and 200 mg/kg dosage, which decreased levels of the blood urea nitrogen, amount lactic acid in the blood, and improved the level of glycogen stored in the liver [47]. It was also reported that the extract of M. officinalis can enhance the anti-fatigue activity [36].

Renoprotective activity
The extract of M. officinalis improved hydrocortisone-induced-KDS-Yang in rats through increasing the interruption of energy and amino acid metabolism and enhancing transmethylation. But it could not modulate the gut microbiota [51]. Some processed products of M. officinalis, including M. officinalis extract, liquorice-processed M. officinalis, salt-steamed M. officinalis and Mornda pulp could also improve the symptoms of KDS-Yang in mice, and the active sequence is: salt-steamed M. officinalis was the most significant improvement on KDS-Yang, next with liquorice-processed M. officinalis, Mornda pulp and M. officinalis extract [52].

Fertility improvement activity
Oligosaccharides of M. officinalis was used to cure impotency by shielding the DNA of sperm cells from being injured by H 2 O 2 [53]. Aqueous extracts of M. officinalis improved the thickness of the epithelium of the tubule, seminiferous tubules with active sperm cells and level of testosterone in the blood, which showed little or no change with levels of follicle-stimulating hormone in the blood and lutropin in rats treated with cyclophosphane. These results indicated that M. officinalis can be beneficial to reproductive organs: which could help in production of matured and active sperm cells and improve secretion of gonad hormones of Leydig cell in cyclophosphamide-inducedtesticular spermatogenic disorder [27].

Cardiovascular protective activity
The oligosaccharides isolated from M. officinalis could protect the cardiac muscle against IRI rats through inhibition of oxidative stress reaction and lipidperoxidation at the dosage of 1.4 and 2.8 g/Kg/day [54]. The ethanol extract of M. officinalis root could eliminate the blood stasis and inhibited the rate clumping together platelets in the blood and improve haemorheological indexes and flowing of blood at the dose of 3, 6, 12 g/Kg bw/day for days [55]. The aqueous extracts of M. officinalis together with vitamin C could reduce the serum urea nitrogen and creatinine, alleviate the superoxide dismutase and decrease the content of malondialdehyde of the swimming rats. Which indicated that M. officinalis combined vitamin C showed a shielding effect on exerciseinduced renal injury in testing rats [56].

Hypoglycemic and hyperglycemic activities
Reports showed that M. officinalis dried roots owned both hypoglycemic and hyperglycemic properties [40]. Ethanolic extract of M. officinalis root decreased the immoderate blood glucose level of streptozotocin-induced-diabetic rats at 150mg/Kg, but those of normal rats increased at 600mg/Kg. n-butanol extract effectively improved the immoderate blood glucose levels of the diabetic rats at a dose 50mg/Kg only within three hours after treatment.

Chemical components
M. officinalis contains various bioactive constituents which show therapeutic effects that can be responsible its pharmacological activity for different ailments. The compounds isolated from M. officinalis are: glycosides, anthraquinones, polysaccharides, mono and oligosaccharides, carboxylic acids and their derivatives and volatile oils [11,18,20,25].

Essential oils
According to Yong reported [83], the volatile components of M. officinalis oil were diisobutyl phthalate (39)

Conclusion and future perspectives
M. officinalis is a blessing to mankind especially to the continents which favour its germination, because of its pharmacological activities. Reports showed that M. officinalis. contained Glycosides, Anthraquinones, Polysaccharides, Mono-and Oligosaccharides, organic acids as the abundant groups of compounds, which responsible for its therapeutic activities such as antioxidant, anti-inflammatory, analgesic, antiosteoporosis, antinociceptive, antidepressant, antimutagenic, antimicrobial, pro-fertility activities, antihepatotoxic and anti-HIV.
Despite the notable therapeutic activities of this plant further studies should be fully conducted on toxicity of all the extracts and isolated compounds of this plant to determine whether they can be used as medicine by animals and humans without no or little negative effects. Also, adequate studies should be on isolation and purification of bioactive compounds with sophisticated instrumentations, because there are still undiscovered bioactive compounds which also responsible for its pharmacological properties.
There should be adequate studies on dose-effects relationship, that should be prescribed to cure each ailment. Further investigations should be made on the plant therapeutic activities and their underlying mechanisms.
Functionalization of isolated compounds should be further emphasized in order to improve their activities efficacy. This can be