Nature, a vast reservoir of pharmacologically active molecules, has been most promising source of drug leads for the cure of various pathological conditions. Formononetin is one of the bioactive isoflavones isolated from different plants mainly from
Natural products have served as an infinite reservoir of various diversified chemical compounds, driving pharmaceutical industries for many years [
Different pharmacological studies on natural products have proclaimed their authenticity as potent anticancer [
Triterpenoid saponins and isoflavones belong to family of amphiphilic glycosides which are naturally present in medicinal plants, herbs, and marine organisms. Saponins and isoflavones have major role in folk medicine due to their biological and pharmacological properties [
Formononetin, an isoflavone isolated from soy bean and red clover, has been known to be endowed with numerous pharmacological attributes such as anticancer [
To date, there is no review on the biological potential of formononetin. This article intends to focus on the researches relevant to the biological and pharmacological activities of Formononetin. The literature is searched via different e-sites like PubMed, Elsevier Science Direct, Springer Link, and related journals. Key words which are used for searching are “Formononetin”, “Formononetin and its biological activities”, “anticancer”, and “natural products”.
Formononetin (Figure
List of plants containing Formononetin and its biological activities.
Plants name | Part used/Extract | Yield of Formononetin | Functions | References | |
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Botanical name | Common name | ||||
| Milk vetch | Roots | 10 mg /200 mg of crude extract | Anti-tumor, Anti-oxidant, Antiviral, Anti-proliferative | [ |
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| Goat’s horn | Flowers | 10 mg /200 mg of crude extract | Anti-tumor, Anti-oxidant, Antiviral, Anti-proliferative | [ |
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| Brazilian red propolis | - | 44.14 | Anti-tumor | [ |
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| Red clover | Above | 0.21–0.59 % (Above ground parts) | Anti-proliferative | [ |
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| Spiny rest harrow | Root | 113.622mg/ 100 g dry plant extract | Beneficial for urinary and bladder infection | [ |
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| Soya bean | - | - | Antioxidant, Anti-inflammatory, Anti-microbial | [ |
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| Yellow leader | Roots | 0.191 | Osteogenic activity, Prevent postmenopausal osteoporosis, Anti-oxidant | [ |
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| Mulethi | Roots | 27.856mg/ 100g | Anti-viral, Hepatoprotective | [ |
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| Chinese licorice | Roots | 5.218 mg/ 100 g | - | [ |
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| Chickpea | Seeds | 14.2 mg/ 150mg | - | [ |
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| Shrubby | Roots | 5mg/ 628g ether-soluble fraction | Immuno-enhancement effects | [ |
| African nutmeg | Bark | 16.2mg/180 g | Apoptosis inducer | [ |
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| Millettia | Stem | 87.5 mg/25.5 g crude extract | Proteasome inhibitory activity | [ |
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| Black cohosh | Rhizome | - | - | [ |
Natural sources of Formononetin.
The biological and pharmacological activities of bioactive compound “Formononetin” are well-documented as antitumor activity, [
Biological activities of Formononetin.
Cancer is uncontrolled proliferation of cells which occurs due to genetic or epigenetic modifications and signaling defects in cells [
Currently, it is documented that about 60% drugs that are used for cure of cancer are derived from natural sources [
Formononetin cytotoxic effects against various cancer types via different signaling pathways.
Uncontrolled divisions of cells are key trait of cancer cells [
Formononetin has been documented to arrest the cell cycle at various stages [
Diagram presenting mechanism of action and molecular targets for Formononetin resulting in chemotherapeutic activity.
It can be summarized that Formononetin causes the arrest the cells at G0/G1 phase but it needs to be investigated whether it has arrested the cellular cycle at G0 or G1 phase. Furthermore, it is interesting for researchers to investigate whether Formononetin could arrest the cells at G2/M or S-phase. Thus, further mechanistic investigations are yet obligatory to understand the mechanisms by which Formononetin arrests the cell cycle in various cancers.
Apoptosis is a systematic and synchronized way of cell death which is peculiarized by different morphological features including formation of blebs on cell membrane, condensation of chromosomes, and fragmentation of nucleus [
Formononetin has emerged as novel agent for its chemotherapeutic activity [
Molecular targets of Formononetin in different types of cancer.
Cancer types | Cell lines | Treatment time | IC50 | Molecular targets | Cell cycle arrest | References |
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Ovarian | ES2,OV90 | 48 h | 40 | p38↑, ERK1/2↓, P90RSK↓, AKT↓, P70S6K↓, ROS↑ | G0/G1 | [ |
SKOV3 | 24 h | 283.5 | caspase3/9↑, Bax/Bcl2↑, MMP-2 | - | [ | |
48 h | 209.3 | |||||
A2780 | 24 h | 310.0 | ||||
48 h | 186.1 | |||||
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Breast | MDA-MB-231, MCF-7, | 24 h | 50 | p-GS3K | - | [ |
MCF-7 WS8 | 48 h | 10 | CYP1A1↓, P450 1A1↑ | - | [ | |
MCF-7 | 24, 48h | 50 | ER | - | [ | |
4T1, MDA-MB-231 | 24 h | 160 | TIMP-2↑, TIMP-1↑, MMP-9↓, MMP-2↓ | - | [ | |
MDA-231, MDA-435 | 24, 48, 72 h | 100 | ER | - | [ | |
MCF-7 | 24, 48, 72 h | 100 | GF1/IGF1R-PI3K/ | - | [ | |
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Colon | SW1116,HCT116 | 24 h | 200 | cyclin D1↓, (MMP)2 | G0/G1 | [ |
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Hepatoma | HuH-7 | 24 h | 20 | - | - | [ |
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Cervical | HeLa, SiHa, CaSKi | 24 h | 25 | ROS↓, JNK | - | [ |
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Laryngeal | Hep-2 | 24, 48 h | 50 and 75 | ROS↓, CdCl2 | G0/G1 | [ |
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Lung | A549 | 48 h | 60 mg/ml | p-Smad 2/3↓, TGF- | - | [ |
A549, NCI-H23 | 24 h | 100 | p53↑, p21↑, cyclin A↓, cyclin D1↓, | G1 | [ | |
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Bladder | T24 | 24 h | 200 | T24 | - | [ |
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Gastric | MGC-803 | - | - | - | - | [ |
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Esophagus | EC-109 | - | - | - | - | [ |
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Prostate | PC3 | 48 h | 1.97 | p-ERK↓, p-JNK↓, c-Myc↓ p-p38↓, cyclin B1↓, cyclin A↓, cyclin D1↓, CDK4↓, Axin↑, | G1 | [ |
DU145, PC3 | 48 h | 200 | Bcl-2↓, RASD1↑, Bax↑, IGF-1 R↓ | - | [ | |
PC3 | 48 h | >12.5 | [ | |||
PC-3, DU145 | 48 h | 80 | AKT /cyclin D1/CDK4↓ | G0/G1 | [ | |
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Nasopharyngeal | CNE2 | 24 h | 1 | Bax↓, bcl-2↑, p-ERK1/2↑ | - | [ |
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Adrenal medulla | PC12 | 24 h | 20 | ROS↑, MDA↓, GSH↓ | - | [ |
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Multiple myeloma | U266, RPMI8226 | 48 h | 100 | STAT3↓, STAT5↓, JAK1↓, JAK2↓, cSrc↓, ROS↑, caspase- | - | [ |
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Osteosarcoma | U2OS | 48 h | 80 | Bax↑, | - | [ |
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Glioma | U87MG, U251MG, T98G | 24,48 h | 100 | E-cadherin | - | [ |
Downregulation↓, Upregulation ↑, Activation
Isoflavonoids have been documented as anticancer agents that inhibit cancer cell proliferation and have antimetastatic effects [
Formononetin reduced the p-AKT, p-P90RSK, p-S6, p-ERK1/2, and p-P70S6K proteins as well as enhancing the levels of p-p38 MAPK to mediate cellular proliferation and apoptosis in OV90 and ES2 cells [
Formononetin with IC50 value 2-6
Formononetin is extracted from different plants such as
In this review article, we have suggested that Formononetin is a good drug candidate with promising pharmacological activities. Various researches have documented the potential applications of Formononetin both
Authors declare that there are no conflicts of interest.
Dongjun Jiang and Rabia Batool made contribution to writing different parts of the manuscript. Azhar Rasul and Ghulam Hussain have made substantial contribution to integration of the data and drafting of the manuscript. Muhammad Mateen Tahir has contributed to acquisition of data. Iqra Sarfraz and Tian Qin designed and generated figures of manuscript. Zeliha Selamoglu and Muhammad Ali have reviewed the manuscript. Xiaomeng Li and Jiang Li have read and approved the final manuscript.
This study was supported by Ministry of Science and Technology, China (no. 2016YFE0128500), National Natural Science Foundation of China (no. 31870758), Jilin Provincial Science and Technology Department (20180414057GH, 20170204009YY), Changchun Science & Technology Department, China (17YJ006; 17YJ001), University S & T Innovation Platform of Jilin Province for Economic Fungi (#2014B-1), the Program for Introducing Talents to Universities (no. B07017), The Nagai Foundation Tokyo, Japan (NFT-R-2018), TWAS-COMSTECH Research Grant (no._17-180 RG/PHA/AS_C), and NRPU Research Grants (8381/Punjab/NRPU/R&D/HEC/2017, 8382/Punjab/NRPU/R&D/HEC/2017). The authors would also like to thank Higher Education Commission (HEC), Pakistan, for providing access to related papers from various journals.