**2. Medicinal/therapeutic properties of hyacinth bean**

Being sessile in nature, plants have to withstand against various adverse climatic conditions to maintain their growth and developmental architecture. The plants are able to survive stressful conditions by synthesising diverse range of secondary metabolites and protease inhibitors that improve their adaptability [13]. Hyacinth bean for example, produces higher level of trypsin inhibitor (14–27 unit/mg) which is a unique property of this orphan legume crop compared to any other major legumes [14]. Like other serine inhibitors, trypsin inhibitor could also function as antifeedant or could also be responsible for strengthening growth, development and productivity by efficiently modulating proteolytic events with in hyacinth bean, mechanism of which has yet to be revealed [15]. Besides this, hyacinth bean also contains wide range of alkaloids, phenols and flavonoids which can be used in treatment of various chronic diseases essentially arthritis, nephritis sepsis as well as skin diseases thus significantly contributing towards human and animal health. All these nutritional and therapeutic properties make hyacinth bean a prime source of food, forage and cash crop in arid and semi-arid areas. However, till date the genes encoding these secondary metabolites are still ambiguous as the crop it self is considered as "orphan crop" for its genome revolution [1]. Further, both conventional and molecular breeding techniques also have been futile in the identification/linking of quantitative trait loci (QTLs) with production of these imperative secondary metabolites [4]. Therefore, all the above information's have reinstated the need to implement advance omics technology for unleashing the genetic constituent of hyacinth bean and to identify genes/proteins involved in the biosynthesis of important secondary metabolites.

#### **2.1 Anti-inflammatory and analgesic properties**

The phytochemicals or secondary metabolites synthesised by various underutilised crops have the potential to boost innate immune response in humans as well as in animals thus providing immunity against infection, injury and irritation [7]. Several lines of literatures have strongly substantiated that various fruits, vegetables and food legumes synthesise various phytochemicals which are effectively exploited for the treatment of anti-inflammatory disorders, however their mechanism of action is still vague and needs to explored [13]. Various legumes such as soybean, mung bean, moth bean including hyacinth bean have diverted the attention of plant science community due to the presence of functional biological compounds which not only have health benefits and can also be simultaneously used for the treatment of various chronic diseases [8]. Researchers have analysed, tested and confirmed that the crude extracts of mung bean, hyacinth bean and soybean checks the synthesis of nitric oxide (NO) which is an inflammatory mediator thus significantly reducing the ear edema in mice caused by up-accumulation of arachidonic acid [16]. Likewise, another researcher evaluated crude extract of *Phaseolus vulgaris* and

hyacinth bean was also effective in controlling the expression of 15-lipooxygenase (15-LOX) thus supressing the release of NO and prostaglandin E2 (PGE2). The limited release of NO and PGE2 further downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) with in the macrophages thus preventing the inflammatory disorder [17]. Overall, the result indicated that ethanolic extract of the above-mentioned beans can effectively modulate anti-inflammatory response by regulating the expressions of anti-inflammatory enzymes and transcription factors [17].

The phenols present in the dry seeds of legumes such as hyacinth bean have also been implicated to exaggerate anti-inflammatory response upon their adequate consumption [18]. A plethora of research have well indicated that seed and other ethanolic extract of food legumes is rich source of polyphenols and natural antioxidants capable of stimulating anti-inflammatory activity by suppressing the expression of 15-LOX as well as modulating the expression of cyclooxygenase −1 (COX-1) and COX-2 [19]. Similar findings have also been reported by Zhu et al. [16] in pinto bean, black bean and common bean where seed extract was effective in regulating the expression of interlukin-6 (IL-6), interferon-γ (IFN- γ) and IL-17A thus effectively ameliorating acute colitis in mice. In addition to phenolic compounds, these legumes also contain lectins which is protein capable of showing anti-inflammatory response after binding reversibly to carbohydrates [20]. For example, lectins isolated and purified from *Clitoria fairchildiana* showed enhanced anti-inflammatory activity against paw edema and reducing it up to 70% in affected mice [21]. Nonetheless, these phytochemicals have also been identified and documented in hyacinth bean which are capable of inducing multitude of immune response against chronic diseases, however, the functional genes/proteins responsible for their synthesis, transport and mechanisms by which they induce immune response needs an in-depth investigation.

#### **2.2 Anti-diabetic properties**

The flavonoids such as flavanones, flavanols, anthocyanidins, flavones and isoflavones present in fruits and vegetables have delineated themselves as key players in the treatment of cardiovascular diseases, diabetes and cancers [22]. Various legumes are also a rich source of dietary flavonoids that can regulate carbohydrate digestion, glucose uptake and insulin signalling via various signalling pathways [23]. Among all the flavonoids, dietary isoflavones *per se.,* daidzein and genistein are abundantly found in leguminous plants [24] found exclusively in soy foods. Increasing evidences have well suggested and evaluated the anti-diabetic properties of both the isoflavones i.e. daidzein and genistein in cell culture studies [24]. Dietary intake of both the isoflavones have been shown to modulate glucose metabolism and insulin levels in Type 1 & 2 diabetes thus exerting anti-diabetic effect by increasing lipid plasma composition and accordingly insulin sensitivity [25]. Concomitantly, another study used soy supplemented diet to control blood glucose level in mice [26]. The result of the study successfully demonstrated that soy food significantly improves lipid profile and glucose metabolism in the mice as direct result of increased phosphorylation of AMP activated protein kinase (AMPK) which in turn have caused favourable metabolic changes upon activation of genes/ proteins involved in fatty acid oxidation pathway in peroxisome [27]. This report is consistent with the previous findings attributing exceptional role of soy food in the modulation of genes/proteins of AMPK pathway thus efficiently controlling blood glucose levels similar to other flavonoids [27].

Some researchers have also reported neutral to moderate effect of soy food and methanolic extract of hyacinth bean rich in isoflavones in controlling plasma lipid

#### *Unlocking Pharmacological and Therapeutic Potential of Hyacinth Bean (*Lablab purpureus *L.)… DOI: http://dx.doi.org/10.5772/intechopen.99345*

profile thereby confirming anti-diabetic effect of isoflavones could act differentially under *in-vitro* and *in-vivo* conditions [28]. For instance, dietary intake of isoflavones prevented the onset of diabetes in rats and improved blood glucose homeostasis by stimulating the function of pancreatic β-cells. Further, the researchers also noticed a sharp increase in insulin/glucagon ratio and C-peptide level in affected mice as compared to normal healthy rats [29]. The possible reason behind improved insulin/glucagon ratio in affected mice that consumed isoflavones could be due to the downregulation of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase beta oxidation. Furthermore, researchers have also indicated that genistein could modulate pancreatic β-cells via distinct metabolic pathways, Ca2+ signalling and calmodulin kinase II pathway [30] thus effectively regulating insulin synthesis in target cells/tissues. The isoflavones such as genistein and daidzein have also been shown to modulate Janus kinase/Signal transduce and activation of transcription (JAK/STAT), ERK-1/2 (serine/threonine protein kinase) and nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) pathways thus stimulating the synthesis cytokinin's in response to pathological alterations [31].

Genistein have also been documented to stimulate the expression of protein kinase A and cAMP cascade which play important role in the proliferation of INS1 and pancreatic β-cells thus efficiently regulating glucose metabolism in mice [31]. However, in addition to isoflavones, anthocyanidin found in soybean seeds rich in cyanidin, delphinidin and petunidin have also demonstrated anti-diabetic effect in streptozotocin induced diabetic rats [32]. Researchers have used methanolic extract of anthocyanidin to diabetic mice and observed that the anthocyanidin effectively raised serum insulin concentration and glucose metabolism in rats. The possible reason behind the anti-diabetic effect of anthocyanidin could be due to the enhance translocation of GLUT4 (glucose transporter) which in turn have stimulated glucose uptake or anthocyanidin could have improved insulin signalling by causing phosphorylation of insulin receptor [33]. Similarly, in another study, researchers have also documented the beneficial effect of anthocyanidin by analysing it on diabetic animal model where they observe that diabetic animal treated with soybean anthocyanidin showed enhanced plasma insulin levels and low triglyceride content [34]. Furthermore, researchers continued their observation up to 12 weeks and observed that the diabetic mice exhibited reduced body weight, blood glucose level, triglyceride levels as revealed by lower expression of lipogenic gene expression in liver and fat [35]. Although, various studies have demonstrated the antidiabetic effect of both isoflavones and anthocyanidin on animal system, there effect on controlling diabetes in humans are still limited. Therefore, efforts are needed to expand the dimension of research involving structural, biochemical and molecular characterisation of important therapeutic compounds obtained from underutilised legume crops for their efficient use in the human and animal welfare.

#### **2.3 Anti-cancerous/tumour properties**

The bioactive peptides found in certain legumes and cereals crops has been implicated to regulate growth and development of crops plants by imparting biotic and abiotic stress tolerance [36]. Further, researchers have also isolated and purified some of the plant bioactive peptides and demonstrated their pivotal impact on human health and immune response [37]. Lunasin, a 43 amino acid peptide initially identified and isolated from soybean has shown its tremendous competency in inhibiting cell division in tumour/cancer cells and protect DNA damage by delaying histone acetylation in mammalian cells under oxidative stress [38]. Later, lunasin was also identified in cereals and pseudo-cereals such as rice, wheat, barley and

amaranth, however, its present in extremely low quantity as compared to soybean [39]. Being a rich source of lunasin, soybean has been extensively investigated in order to get valuable insight into its structure and function properties, mode action in preventing cancer and the ecological factors that can influence its biosynthesis and transport [37]. Initially, lunasin was identified as chemo-preventive agent but in-depth investigations by several researchers demonstrated that lunasin can effectively suppress skin tumorigenesis in mouse by delaying foci formation in DMBA NIH/3 T3 cells [40].

In addition, researchers have also well documented the chemo-preventive property of lunasin in breast cancer affected mice where they observed significant reduction (30–40%) in tumour cells after treating the mice with lunasin for two months [37]. However, not much research has been focused on lunasin therapeutic properties in soybean as well as in other underutilised legumes still researchers have hypothesised its broad-spectrum role in the treatment of lung cancer, colon cancer and leukaemia [36]. One of the possible mechanisms by which lunasin block cell division in cancer cells could be due to its ability inhibits cell cycle at G2 phase thereby inducing apoptosis in the affected cells [40]. Initial studies on lunasin's mode of action revealed that it can bind to hypoacetylated histone cores in cancer cells and inhibit acetylation in breast cancer cells and prostrate cancer cells [37]. Recently, researchers have made striking discovery claiming that lunasin binding can suppress the integrin signalling in cancer/tumour cells thereby inhibiting focal adhesion kinase/protein kinase B (FAK/AKT) and extracellular signal-regulated kinase 1 (ERK1) signalling in cancer cells [41]. Certain plant protease inhibitors such as Bowman-Birk inhibitors and flavonoids such as flavon-3-ols found in soybean and other legumes have also demonstrated their role in controlling breast and colon cancer [41]. However, detailed characterisation of their structural and functional properties in many legume crops is still ambiguous and need extensive research by employing advance omics technology for their potential application.
