Systematic Review of Chemical Compounds with Immunomodulatory Action Isolated from African Medicinal Plants

Abstract

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw^® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.

Keywords: immunomodulators; medicinal plants; phytochemicals; transduction mechanisms.

Figure 1

PRISMA flow diagram of the study selection.

Figure 2

Plant- derived immunomodulators. The isolated phytochemicals with immunomodulatory activities include polyphenols (carbohydrates, alkaloids, and proteins). * NB: Astragalus VII and Macrophyllosaponin B were isolated from the Astragalus genius in particular Astragalus trojanus Stev. and Astragalus oleifolius DC, which are not distributed in Africa.

Figure 3

Structures of the identified alkaloids with immunomodulatory activities. The isolated alkaloids comprise a protoberberine isoquinoleic (1), aporphine isoquinoleine alkaloids (2–5), and a piperidine alkaloid (6). They have common scaffold highlighted in red. All have been tested and showed immunomodulatory activities.

Figure 4

Structures of identified terpenoids with immunomodulatory activities. These terpenoids are distinguished in triterpenoid pentacyclic saponin (7, 8, 9, 13, 20, 21), lactone sesquiterpenoid (10, 11, 12), tetracyclic saponin heterosid (14, 15, 16, 17), pentacyclic saponin heterosid (18), diterpenoid (19) and Acyclic monoterpenoid (22). They have in common adjacent 2–5 rings, except for linalool (22). It is an advantage to have simple and complex structures like in linalool and beta-aescin (18), respectively, exhibiting immunomodulatory activities, which will lengthen the list of analogues.

Figure 5

The structures of identified polyphenols acting as immunomodulators. The isolated polyphenols include flavonoids with the scaffold highlighted in red, polyphenolic acids with the acid group highlighted in blue, and ceto-phenolics. The thymoquinone is classed among polyphenols because in vivo metabolism gives phenolic compounds. The sugar group (highlighted in pink) is critical in the structure–activity relationship of flavonoids. Nevertheless, the active molecules have shown a similar way of modulating the immune system. They comprise phenol acid (38), cinnamic acid (23, 34–37), lignan (30), flavonols (25, 28, 39), flavones (33, 42, 43), flavanone (41), heterosid flavonols (24, 26, 27, 29, 31, 32, 40), heterosid flavones (33′, 44), and other phenolic compounds (45, 46).

Figure 6

Structures of African medicinal isolated coumarins acting as immunomodulators. Sesquiterpenyl coumarins (48–49) with a long carbon chain show an identical mechanism of action while simple coumarin (47) has a different mechanism of action. The coumarin basic core is in red.

Figure 7

Structures of identified glycosides acting as immunomodulators. They comprise monosaccharides (50, 54, 55, 56), disaccharides (53) and aglycans (51, 52). The activity of glycosides is not linked only to the structure of the sugar unit (represented in red), but the aglycan part plays an important role. For example, the 11-hydroxymustakone molecule, without a sugar unit, has comparable activity to that of tinocordiside and cordifolioside.

Figure 8

Immunomodulatory signal-transduction pathways of some molecules. TLR: toll-like receptor; MyD88: myeloid differentiation primary response gene 88; MAPKs: mitogen-activated protein kinases; P13k-Akt: phosphatidylinositol-3-kinase-kinase B protein; Ik-Bk: inhibitory kappa B kinase; IKK: I-kB kinase; p38, p50, p65: proteins 38, 50, 65; P: phosphate; NF-kB: nuclear factor kappa B; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; : activation or stimulation by phytochemical; : inhibition or reduction by phytochemical; →: transduction way or activation.