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\def\RunningAuthor{Vadivelan Ramachandran et al.}
\firstPage{2463}
\articleType{Original Article}
\receivedDate{23 Oct 2020}
\acceptedDate{25 Nov 2020}
\revisedDate{10 Nov 2020}
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\journalDoi{ijrps.v11iSPL4.4499}
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\title{Potential Health Benefit Of Isoflavones}
\author{Vadivelan~Ramachandran\textsuperscript{*}\textsuperscript{1},  
            Bhargav~Bhongiri\textsuperscript{1},  
            Raju~Bairi\textsuperscript{1}, 
            Raman~Suresh~Kumar\textsuperscript{2}~\\[5pt]{\textsuperscript{1}Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education \& Research, Ooty, Nilgiris, Tamil Nadu, India}~\\{\textsuperscript{2}Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education \& Research, Ooty, Nilgiris, Tamil Nadu, India}}

\begin{abstract}
Isoflavones are bioactive compounds and structurally related to 17-\ensuremath{\beta }-estradiol  having mild estrogenic character also known phytoestrogen. These are available in more quantities in vegetables like green beans, soybeans, mung beans. In grains, they are available for the most part as glycosides, which are absorbed very poorly. It can behave as estrogen agonists or antagonist, by depending on the estrogenic level of endocrine, yet the action of isoflavones are complex because of numerous factors, for example, compound structures and mode of action. Though foods rich in isoflavones have become a centre of interest because of their beneficial effect on many health issues. In view of the appraisal of these illnesses by the action of isoflavones, it was fulfilled that the ability of isoflavones in the anticipation and management of different ailments generally results from their phytoestrogen antioxidant action. Isoflavones were called to as mysterious biological compounds that characteristic to forestall many major health issues. Intake of soy product has been connected to a decrease in rate or seriousness of long term illness, for example, heart disorder, breast and prostate malignancies, menopausal symptoms, bone disorder, so forth. This review discussed an overview of its health benefit on different human diseases.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Isoflavones,\newline Bioactive Compounds,\newline Chronic disease,\newline Health Benefits
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Vadivelan~Ramachandran~\\ Phone:\ +91 9047539532~\\  Email:\ vadivelanr@jssuni.edu.in
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
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\section{Introduction}
Isoflavones are polyphenol type of bioactive compounds and non-steroidal in nature. They are wildly found in soybeans and other legumes like chickpeas, fava beans, pistachios, peanuts, other fruits, nuts. The biological activity of isoflavones has been recognized all across the globe. These compounds are also known as phytoestrogens due to their estrogenic activity \unskip~\citep{938836:20815765}. From a chemical point of view, these are structurally similar to mammalian estrogen having mild estrogenic activity. It is also a subclass of flavonoids present in plants and has potent antioxidant properties. The structure of isoflavones is related to 17\ensuremath{\beta }-estradiol and produces both estrogenic and antioxidant functions. 

So many research and review published reveals the health benefit and importance of isoflavonoids in cure of numerous diseases like menopausal symptoms \unskip~\citep{938836:20815788}, Prostate Malignacy \unskip~\citep{938836:20815766}, Heart Diseases \unskip~\citep{938836:20815463}, Osteoporosis \unskip~\citep{938836:20815805}, obesity and diabetics \unskip~\citep{938836:20815798}, Cognitive function \unskip~\citep{938836:20815467} and viral infection \unskip~\citep{938836:20815389}. Digramatic representation of health benefits of isoflavones is shown in Figure~\ref{f-768ce4501037}.


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\caption{\boldmath {Health benefits of isoflavones}}
\label{f-768ce4501037}
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Isoflavones are biosynthesized in vegetables, for example, soy, mung bean sprouts, naval force beans, red clover, Kudzu, however, is plentiful in soybeans. Most members of the family Fabaceae contain more quantity of isoflavones. The major diet rich in isoflavones are soybeans, soy powder, soy chips, confined soy protein, soy nourishments traditional, (for example soy milk), and  miso, Tempeh soybean paste, soy sauce and natto.

\textbf{Chemistry }

Isoflavones are valuable and biologically active compounds of the flavonoid group. Chemically these are consists of an estrogenic compound esradiol nucleus. These are biosynthesized through phenylpropanoid pathways and yield two main chalcones like nringenin and 4,2,4'{\textendash} trihydroxychalcones and in the presence of the enzyme 2-hydroxy isoflavone synthase, it yields daidzein, genistein and glycetin{\textemdash}these on interaction with Uridine diphosphate glucunosyl transferases (UGT) yield daidzin, genistin and glycitin respectively. Interaction of malonyl transferase gives malonyl derivatives \unskip~\citep{938836:20815456}.

\textbf{Bioavailability }

Isoflavones in food are metabolized in the intestine to the active metabolite equol which possesses more estrogenic activity than daidzein. Equol has an affinity towards estrogen receptor ER\ensuremath{\alpha } and ER\ensuremath{\beta } \unskip~\citep{938836:20815791}. 

\textbf{Health Benefits}

\textbf{As antioxidants}

Genistein produces antioxidant activity by inhibiting radicals and Genistein has cancer prevention agent properties as a forager of radicals and chelates of metals. It shows antioxidant action by interfering with gene expression of enzymes which interact with the bio-antioxidant like superoxide dismutase (SOD) and catalase (CAT) and prevent the formation of secondary oxidants H\ensuremath{_{2}}O\ensuremath{_{2}} and hypochlorous acids \unskip~\citep{938836:20815468}. The OH group at C-5 make Genistein as an extra potent antioxidant than daidzein and equol are more potent than its bio-precursor as there is an absence of 2,3-double bond and 4-oxo group \unskip~\citep{938836:20815390}. The metabolites of isoflavones equol, 8-hydoxy daidzein, O-DMA and trihydroxy benzene also sows potent antioxidant action. Among them, 8-hydroxy-daidzein is more active against hydroxyl and superoxide anion radicals. These metabolites are good chelating agents for ferrous compounds compared to genistein and daidzein, by reacting with lipid radicals isoflavones able to diminishes oxidation of LDL and lipid peroxidation.

\textbf{Isoflavones in cancer}

Genistein inhibits protein tyrosine kinase (PTKs) catalyzes the phosphate (PO43-) addition to protein and other compounds from tyrosine which enacts or deactivates wide range proteins and enzymes, particularly in carcinogenesis. PTKs are exceptionally expressed in prostate, breast, stomach malignant growths, and a few areas of the brain, for example, the hippocampus. At high doses, isoflavones stop PTK activities in these tissues, which decrease the tumorigenesis and neuronal degradation. Additionally, restraint of PTK action may cause improving cardiac Activities \unskip~\citep{938836:20815459}.

Studies revealed that for gene expression in tumorigenesis, insulin reactivity, in carbohydrate, lipid and protein metabolism isoflavone act as a regulating factor. Its effect on the cardiovascular system by in vitro was examined on different isolated cardiac portion and cardiac cells and it was noticed that isoflavones produce raise in prostacyclin, endothelial nitric oxide synthase stimulation, inhibition of cell prolipheration, inhibition of DNA synthesis, relaxation of blood vessels and reduction of plaque \unskip~\citep{938836:20815454}. A past report by Akaza \unskip~\citep{938836:20815388} was the early report to affirm the relationship between prostate malignant growth and isoflavone consumption.No persuading clinical confirmation or proof that genistein might be useful in prostate malignancy treatment \unskip~\citep{938836:20815766}. In between 2008 and 2012 years, studies noted a noteworthy relationship of isoflavones with a diminished danger of prostate cancer and daidzein changed over to equol by intestinal microorganisms prompts an essentially decreased danger of prostate gland cancer \unskip~\citep{938836:20815792}.

\textbf{Isoflavones in cardiovascular diseases}

From many clinical studies, it was observed that when soy isoflavonones was intake with diet it there was significantly lowering in total cholesterol, LDL-cholesterol and triglyceride in blood and reduce the risk of cardiovascular diseases in both healthy individuals and treat individuals. As isoflavones contain minimal fat which is a saturated and good content of fatty acid, it can improve endothelial activities and decrease the development of atherosclerosis \unskip~\citep{938836:20815794}.

Biomarkers that reflect both administration and metabolism might be ɱore enlightening than self-reports of food intake. Studies found that equal active metabolite of daidzein contrarily connected with the danger of coronary heart disease (CHD) in a female. Isoflavones show agonist effect on estrogen in the cardiovascular system at low endocrine estrogen level by interacting with ER-\ensuremath{\beta } receptor. Isoflavones also act as blood vessel relaxant by promoting prostacyclin release and inhibiting collagen-induced aggregation and platelet activation to produce anti-inflammatory action and formation of plaques in blood vessels. Isoflavones also reduce the level of LDL on endothelial cells. But the function of total cholesterol and triglycerides are questionable \unskip~\citep{938836:20815454}. 

The hypothesis of an ex-vivo study was isoflavones raise the oxidation resistance and antiproliferative potency of LDL which is its antiatherogenic properties. It was observed in another study that in case of an atherosclerosis patient a 12-week intake of isoflavones there was a decrease in high sensitive C receptive protein in serum, improvement in brachial flow-mediated dilation \unskip~\citep{938836:20815457}.

\textbf{Isoflavones in diabetes}

From many of the studies, it was noted that genistein produces antidiabetic action by directly interact with \ensuremath{\beta }-cell proliferation, insulin release and inhibiting apoptosis, also by indirectly acting as ER agonist, as an antioxidant and inhibiting tyrosine kinase \unskip~\citep{938836:20815460}. 

A limited data are there about the impact of genistein intake in diabetic patients, but many studies on animal and cell culture have reported at physiologically relevant dose genistein produce a direct effect on \ensuremath{\beta }-cells \unskip~\citep{938836:20815793}. It was also noticed that the fermented soy products prevented the development of type 2 diabetic in a better way than non-fermented one \unskip~\citep{938836:20815462}. 

\textbf{Isoflavones in osteoporosis}

Regular or surgical menopause brings about an underlying period of osteoporosis followed by a time of slower skeletal crumbling. This rapid bone loss happens inside the initial 10 yrs following the ending of menses or ovariectomy. The lack of ovarian hormone related with menopause brings about an expanded rate of bone turnover and prompts unevenness among restoration and formation, along with these quickening bone losses \unskip~\citep{938836:20815787}. 

\textbf{Isoflavones in menopausal syndrome  }

Dietary soy items have marginally and unobtrusively diminished climacteric vasomotor manifestations influencing hot flushes in menopausal ladies comparative with fake treatment \unskip~\citep{938836:20815788}. 

\textbf{Isoflavones in learning and memory}

Lee observed isoflavones could interfere with the cholinergic system of the brain and minimize nerve damage due to ageing in the male rat. Several mechanisms proposed about the neuroprotective action of isoflavones. Genistein prevents the H\ensuremath{_{2}}O\ensuremath{_{2}} produce toxicity in cells which may cause neuron damage \unskip~\citep{938836:20815464}. It crosses BBB and produces antioxidant properties against UV radiation and chemicals. It was observed soy isoflavones able to enhance the learning and memory in menopausal female \unskip~\citep{938836:20815461}.

\textbf{Isoflavones and immunity }

Isoflavones influence immune function by means of its estrogenic action and protein tyrosine kinase inhibiting properties. Due to the estrogenic action, genistein able to suppresses asthma induced by antigen and autoimmune diseases. Estrogenic property of genistein inflects the ERs mediated immune function. Daidzein the isoflavone able to increase IL-4 production inactivate T-cells and improve the phagocytic reaction of peritoneal macrophages. It also controls hypersensitive reaction by increasing IL-4 production in T cells \unskip~\citep{938836:20815790}. 
    
\section{Conclusions}
In the present article, the activities and functions of isoflavones on several diseases were discussed, which include antimenopausal osteoporosis and antiaging, improvement of learning and memory skills of menopausal women, preven\-tion and management of heart disease, diabetes, antitumor and kidney disease. In view of the appraisal of these illnesses by the action of isoflavones, it was fulfilled that the ability of isoflavones in the anticipation and management of different ailments generally results from their phytooestrogen antioxidant action. Despite the fact that isoflavones have been exhibited to apply beneficial impacts on the prevention and treatment of several illnesses, conceivable antagonistic responses have as of late become the focus of consideration. Hence, more clinical preliminaries are enquired to assess the impacts of isoflavones on the prevention of diseases and their role in the management of different diseases, either alone or with ordinary remedial methods.
\section*{Acknowledgement}Authors wish to thank DST-FIST, New Delhi for their infrastructure support to Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, P.B. 20, Rocklands, Ooty- 643001, Tamilnadu, India and funding support from JSS AHER.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.

\textbf{Funding Support }

The authors declare that they have no funding support for this study.
    

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