The effect Moringa oleifera Lam in Immune Disorders: A clinical study
The present study was carried out to investigate the efficacy and safety of Moringa oleifera Lam in Immune Disorders.
Introduction
Moringa oleifera Lam (MO), a frost and drought-resistant plant of the monogeneric family Moringaceae, a native plant of tropical forests of India, is characterized by its versatile applications as a food additive and supplement therapy (Anwar et al., 2007). MO is suitable for food application because of its abundant nutritional ingredients, such as essential amino acids, oleic acids, vitamins, and minerals. MO is recognized for its medicinal uses, such as treating various infections, modulating the immune system, and displaying anti-oxidant, anti-diabetic, or anti-tumor effects (Dhakad et al., 2019).
Moringa tree leaves were mostly used for cattle feed in ancient times (Sun et al., 2017), but were gradually started to be used in the human diet to maintain mental and skin health (Anwar et al., 2007). With its growing popularity, different parts of MO, such as roots, seeds, and pods, were recognized as nutritious and medically valuable. Currently, MO is widely used in food ingredients, nutraceuticals, and medications and has been termed a €œMiracle tree€ (Dhakad et al., 2019).
Bioactive Constituents and General Function of Moringa oleifera
The bioactive constituents of MO have been identified in almost all parts of the plant (Liang et al., 2019). The specific constituents isolated from MO mainly (detailed in Supplementary Table S1) include flavanoids (mainly distributed in the leaves), glucosinolate and isothiocyanate (mainly distributed in the leaves), phenolic acid (all distributed in the leaves), alkaloids and sterols (distributed in the leaves, roots, and seeds), and terpene (all distributed in the pods) (Anwar et al., 2007; Bichi, 2013; Baldisserotto et al., 2018; Dhakad et al., 2019). The constituents of the leaves and seeds were most frequently reported. Based on the phytochemical analysis, phenols and alkaloids are more abundant in the leaves than in the seeds, while flavonoids, saponins, and anthocyanins are more abundant in the seeds (Gupta et al., 2018). Besides, other kinds of nutrients are present in high levels in the processed products of MO, including a number of fatty acids derived from the seed oil (Leone et al., 2016), various kinds of minerals from the dried leaf powder (Witt, 2014), and high-quality carbohydrates from refined gum exudates (Kar et al., 2013; Gupta et al., 2018).
The addition of a small amount of MO is reported to significantly improve the nutritional value of food such as bread, yoghurt, cheese, and soup (Williams, 2013; Stadtlander and Becker, 2017). The diverse parts of MO have been processed into many food products in more than eighty countries, to improve mineral and vitamin deficiencies (Ali et al., 2017). Moreover, few side effects have been reported for the use of MO (Bichi, 2013; Palada et al., 2017; Dhakad et al., 2019).
Results
Rheumatoid arthritis (RA) is a typical auto-immune disorder, characterized by an increase in pro-inflammatory cytokines (including TNF-α, IL-6, and IL-1β) and inducible inflammation-related enzymes (such as cyclooxygenase and lipoxygenase) and a decrease in anti-inflammatory cytokines (as IL-4 and IL-10). Several studies have reported the efficacy of MO in alleviating joint inflammation associated with RA; however, the exact mechanism remains unknown (Mahajan et al., 2007; Padmini et al., 2016). Saleem and colleagues used complete Freund's adjuvant to establish an RA model in rats. In the model, treatment with a MO methanolic extract markedly reduced the serum concentration of C-reactive protein, prostaglandin E2, and TNFα, markedly downregulated the levels of NF-κB, prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), and IL-1β, and significantly upregulated the mRNA levels of I-κB, IL4, and IL-10, and remarkably restored the histopathological indices and arthritic index in the joints (Saleem et al., 2019).
Atopic dermatitis (AD), a kind of chronic, inflammatory skin disease, belongs to another group of classic auto-immune disorders (Brunello, 2018). It is generally accepted that AD is typically accompanied by an extreme initiation of T-cells, elevated serum IgE levels, and the skin infiltration of dendritic cells and T cells (Yamura et al., 1981). Choi et al. used TNF-α and IFN-γ to induce AD in HaCaT cells (human keratinocytes), and applied a Dermatophagoides farinae extract to monitor AD in BALB/c mice (Choi et al., 2016). MO not only reduced the expression of pro-inflammatory cytokine-related mRNAs and the levels of mitogen-activated protein kinases (MAPKS) in vitro, but also improved the ear skin thickness and serum immunoglobulin levels in vivo. In addition, a decrease in retinoic acid-related orphan receptor γT (RORγT) levels was observed, which regulates the expression and development of Th17 cells). Levels of thymic stromal lymphopoietin (TSLP, which triggers dendritic cells and secretion of Th2 cytokine production) and mannose Receptor C-Type 1 (CD206, which is expressed in various immunological cells) were also reduced. These results strongly suggested the efficacy of MO as a supplement to treat patients with AD.
Conclusion
Current research shows that MO exerts its multiple immune-related effects primarily through directly eliminating pathogens or modulating the balance of pro- and anti-inflammatory mediators released from various kinds of immune cells by regulating the activity of signaling pathways, such as the canonical NF-κB pathway (Figure 1). Significantly, the bioactivity of MO is dependent on its active ingredients, which are related to the different parts of this plant and extraction methods used. Notably, in some experiments, low-dose application of MO might have a better anti-inflammatory effect than higher doses (Ferreira et al., 2008; Almatrafi et al., 2017; Kapse et al., 2017), which suggested the necessity of identifying the appropriate dosage of MO before clinical application.
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