Research Progress on the Pharmacological Activities of Oligosaccharides and Polysaccharides from Morinda officinalis

Morinda officinalis, also known as Bajitian, Tuerchang, Jiyanteng, Heitengzuan, and Jichangfeng, is a perennial climbing woody vine belonging to the Rubiaceae family and the Morinda genus. Its fleshy roots are used medicinally and are considered one of the four famous southern Chinese medicinal materials. It is distributed in Guangdong, Fujian, Guangxi, Hainan, and other regions, with Deqing, Guangdong widely recognized as its genuine producing area. Modern chemical research has shown that Morinda officinalis contains various chemical components such as sugars, anthraquinones, iridoids, flavonoids, amino acids, and trace elements. Among them, Morinda officinalis has a high sugar content, including monosaccharides, oligosaccharides, and polysaccharides, which serve as the essential material basis for its medicinal effects.

Morinda officinalis Oligosaccharides

Oligosaccharides, often referred to as inulin-type oligosaccharides, are low-molecular-weight polysaccharides consisting of 2 to 10 monosaccharides linked by glycosidic bonds. Research indicates that oligosaccharides from Morinda officinalis possess various pharmacological activities such as anti-stress, anti-depression, promoting spermatogenesis, scavenging reactive oxygen species, and protecting against myocardial ischemia-reperfusion injury. Specifically, oligosaccharides like kestose, neokestose, 1F-fructosylneokestose, and nystose can serve as indicators for quality control of Morinda officinalis medicinal materials.

1. Antidepressant Effect

Scholars have employed the chronic unpredictable stress method to establish a depression model in male SD rats. Using Morinda officinalis oligosaccharides and fluoxetine as comparators, they observed behavioral changes in rats through the sucrose preference test and forced swimming test. The results showed that Morinda officinalis oligosaccharides could enhance the rats' preference for sucrose solution and significantly reduce their immobility time during forced swimming, indicating its antidepressant effect. Furthermore, when detected using Western blot analysis, the high-dose group of Morinda officinalis oligosaccharides significantly increased the expression of BDNF (Brain-Derived Neurotrophic Factor) and Synapsin1 in the hippocampus of the model rats. The potential mechanism may involve modulating the BDNF pathway and synaptic plasticity. Additionally, evaluations using the single prolonged stress (SPS) model revealed that Morinda officinalis inulin-type oligosaccharides could reverse the behavioral deficits in SPS-treated rats, reducing the freezing time in the contextual fear paradigm without affecting their normal activity in the open field. These oligosaccharides also increased the levels of allopregnanolone in the prefrontal cortex, hippocampus, and amygdala, suggesting that the anti-post-traumatic stress disorder (PTSD) effect of Morinda officinalis inulin-type oligosaccharides is related to allopregnanolone synthesis.

2. Improvement of Reproductive Function

Using a model of cyclophosphamide (CTX)-induced sperm reduction in male mice, with the methyltestosterone group as the positive control, experiments were conducted with Morinda officinalis aqueous extract, 80% ethanol extract, and oligosaccharide crystal groups as the treatment groups. After administration, sperm count, sperm motility, and sperm deformity rate were examined. Compared to the model group, all three treatment groups showed increased sperm count and motility, with the strength of the effect following the order of Morinda officinalis oligosaccharide crystals, 80% ethanol extract, and aqueous extract. This indicates that Morinda officinalis oligosaccharides may serve as the fundamental substance promoting spermatogenesis.

To establish a yang deficiency mouse model through "excessive fatigue and irregular sexual activity," high-dose treatment was administered for six weeks. It was found that FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone), T (Testosterone), and GnRH (Gonadotropin-Releasing Hormone) levels were significantly elevated, suggesting that Morinda officinalis oligosaccharides may improve reproductive function by regulating the pituitary-hypothalamus-gonadal axis.

3. Anti-inflammatory Effect

Using rat uterine ischemia-reperfusion injury as an inflammatory model, Morinda officinalis oligosaccharide solution was administered, and the levels of TNF-α, IL-1β, IL-6, and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of these inflammatory cytokines were reduced in all three gradient dosing groups, indicating that Morinda officinalis oligosaccharides can alleviate the inflammatory response following uterine ischemia-reperfusion injury, thereby protecting the uterus and reducing the damage caused by ischemia-reperfusion.

4. Promotion of Angiogenesis

Using the chick chorioallantoic membrane (CAM) model and the rat acute myocardial infarction (AMI) model, with Shexiang Baoxin Pills as the positive control, experiments revealed that in the Morinda officinalis oligosaccharide-containing serum group and the basic fibroblast growth factor (bFGF) group, small vessels grew radially from the carrier center, exhibiting significant growth. Compared to the AMI model group, the medium and high-dose groups of Morinda officinalis oligosaccharides significantly increased microvascular density (MVD) and the optical density values of vascular endothelial growth factor (VEGF) and bFGF. However, their effect was weaker than that of the Shexiang Baoxin Pills group. These findings indicate that Morinda officinalis oligosaccharides can not only promote angiogenesis in CAM but also enhance angiogenesis in ischemic myocardium post-AMI in rats, thereby improving local collateral circulation in ischemic myocardium. The mechanism is related to the regulation of VEGF and bFGF protein expression in ischemic myocardium post-AMI.

Morinda Officinalis Polysaccharides

Polysaccharides, as one of the major active components of Morinda officinalis, exhibit notable biological activities in various aspects such as antioxidant, antifatigue, immunomodulatory, and anti-osteoporotic effects, making them promising candidates for further development.

1. Antioxidant Activity

Morinda officinalis polysaccharides possess the ability to scavenge free radicals, demonstrating significant antioxidant activity. Their half-maximal inhibitory concentrations (IC50) for scavenging hydroxyl radicals and H2O2 are 1.40 mg·mL-1 and 2.81 mg·mL-1, respectively, indicating good antioxidant activity. At the same concentration, the antioxidant capacity of Morinda officinalis polysaccharides is comparable to or slightly lower than that of vitamin C (VC). Animal studies have found that administering Morinda officinalis polysaccharides to ovariectomized rats significantly reduces serum malondialdehyde levels and enhances the activities of red blood cell superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity, further confirming their potent antioxidant effects.

2. Anti-Osteoporotic Effects

Research has shown that Morinda officinalis polysaccharides can increase the secretion of type I collagen and osteocalcin, elevate alkaline phosphatase activity, promote the expression of osteoblast transforming growth factor β1 mRNA and core-binding factor α1 (Cbfα1) mRNA, downregulate the expression of osteoblast DKK-1 protein, upregulate the expression of osteoprotegerin (OPG) mRNA and protein, and downregulate the expression of receptor activator of nuclear factor-κB (RANKL) mRNA and protein, thereby influencing bone metabolism. The uniform polysaccharides MOW90-1 and MOP70-2 from Morinda officinalis can upregulate the expression of osteoblast-related factors such as Runt-related transcription factor 2, osteocalcin, osteopontin, and osteoprotegerin, promoting the proliferation, differentiation, and mineralization of osteoblasts. Morinda officinalis polysaccharides significantly upregulate the expression of the anti-apoptotic gene Bcl-2 and downregulate the expression of the pro-apoptotic gene Bax, inhibiting all-trans retinoic acid-induced osteoblast apoptosis. They can also promote the proliferation of rat bone marrow mesenchymal stem cells, increase alkaline phosphatase activity, increase the number of mineralized nodules, and upregulate Cbfα1 mRNA expression, indicating that Morinda officinalis polysaccharides can enhance the differentiation of bone marrow mesenchymal stem cells into osteoblasts. Furthermore, Morinda officinalis polysaccharides can increase bone mineral density, bone mineral content, 1,25-dihydroxyvitamin D, and osteocalcin levels in ovariectomized rats with osteoporosis, elevate serum trace element levels, reduce the expression of serum cytokines IL-6 and TNF-α, increase serum levels of 5-hydroxytryptamine and vascular endothelial growth factor, upregulate OPG mRNA expression, downregulate RANKL mRNA expression, reduce the RANKL/OPG ratio, and improve osteoporosis caused by estrogen deficiency.

3. Immunomodulatory Effects

Morinda officinalis polysaccharides possess the ability to enhance the function of immune organs and immune cells, exerting a regulatory effect on the immune system. Compared to the group with impaired immune function induced by cyclophosphamide, crude polysaccharides and column chromatography-purified MOPI-3 from Morinda officinalis significantly increased the immune organ index, macrophage phagocytic rate, and peripheral blood lymphocyte transformation rate in mice, markedly enhancing their immune activity. Furthermore, Morinda officinalis polysaccharides promote the protein expression of monocyte chemoattractant protein-1 and interleukin (IL)-8 in Beagle dog hepatic stellate cell slices, modulating immune function.

4. Regulation of Spermatogenesis

Morinda officinalis is renowned for its kidney-yang tonifying properties, and its polysaccharides specifically contribute to promoting spermatogenesis and repairing spermatogenic disorders. When administered to rats with varicocele, crude polysaccharides from Morinda officinalis increased sperm count, improved the structure of the seminiferous epithelium, stimulated the synthesis and release of gonadotropin-releasing hormone in the hypothalamus, and promoted the secretion of follicle-stimulating hormone, thereby restoring the spermatogenic capacity of the rat testes.

5. Anti-Fatigue Effects

Exercise primarily relies on glycolysis for energy production, which generates blood lactate, while protein and amino acid metabolism produce urea. Consequently, exhaustion time, serum urea nitrogen, and lactate levels can reflect the degree of fatigue. Morinda officinalis polysaccharides significantly prolong the weight-bearing swimming time of mice, reduce serum urea nitrogen and lactate levels, and increase liver glycogen content, demonstrating their potent anti-fatigue effects.

The oligosaccharides and polysaccharides derived from Morinda officinalis contribute to the functioning of the nervous, immune, endocrine, and cardiovascular systems, presenting broad application prospects in the fields of pharmaceuticals and functional foods. However, the low extraction rates and the difficulties in separation and purification of Morinda officinalis oligosaccharides and polysaccharides have hindered their further development. Consequently, there is a need to improve the extraction efficiency of these compounds, strengthen research on their separation, purification, and structure-activity relationships, and provide guidance for the development of Morinda officinalis oligosaccharides and polysaccharides in functional foods and pharmaceutical products.

References:

[1] Li, Xinjie, Li, Lingling, & Lu, Yi. "Research Progress on Purification Technology and Pharmacological Effects of Oligosaccharides from Morinda officinalis." Natural Product Research and Development, 2019, 31(02): 345-353.

[2] Shen, Jie, Ma, Enyao, Zhao, Zhimin, Yang, Depo, & Xu, Xinjun. "Research Progress on Extraction, Separation, and Biological Activities of Polysaccharides from Morinda officinalis." Traditional Chinese Drug Research and Clinical Pharmacology, 2020, 31(02): 246-250.

About the Author

Xiaonisha, a food technology professional holding a Master's degree in Food Science, is currently employed at a prominent domestic pharmaceutical research and development company. Her primary focus lies in the development and research of nutritional foods, where she contributes her expertise and passion to create innovative products.