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Future Journal of Pharmaceutical Sciences
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Therapeutic benefits of gossypin as an emerging phytoconstituents of Hibiscus spp.: a critical review

Future Journal of Pharmaceutical Sciences volume 9, Article number: 95 (2023) Cite this article

Abstract

Background

Flavonoids are one of the crucial secondary metabolites as several functions are carried out by flavonoids, including regulating cell growth, luring insects and pollinators, and defending against biotic and abiotic stressors. They are found in fruits, whole grains, vegetables, spices, tea, wine, herbs, and seeds. More than 4000 flavonoid compounds have been discovered and extracted through different techniques. Most flavonoids are frequently utilized in pharmaceuticals, nutraceuticals, cosmetics, and other products. A flavonol glucoside called gossypin is the primary phytochemical of herbs that comes under the "Malvaceae" family and can be found in many species, including Hibiscus esculentus, Gossypium indicum, and Hibiscus vitifolius, all have it in their flowers. Gossypin shows not only significant pharmacological activities but also a defence mechanism and protects against pathogens, UV radiation, etc. It has drawn much interest from researchers and scholars due to its benefits of few adverse effects, high efficacy, and simple preparation. Thus, the current review focuses primarily on the pharmacological accounts of gossypin in various acute and chronic diseases. The various assays and animal studies conducted in the past supported gossypin effects as supporting the concept of the objective of the title. The review also highlights various patents filled on gossypin’s importance and current market scenario.

Conclusion

Therefore, the technical contents based on pharmacological activities, patents and current market scenario provided in this paper for the improvement of research in numerous scientific fields will be helpful to researchers for suitable alternative designs of gossypin in various disorders.

Graphical abstract

Background

Medicinal plants have always been crucial to the advancement of human health. More than 80% of the global population, according to the World Health Organization, is dependent on healing plants to preserve their wellness and alleviate illnesses [1,2,3]. More than 8,000 different types of medicinal herbs are native to India, as reported by the Botanical Survey of India. Traditional medical practices have a long history in the nation, and current study on medicinal plants is ongoing due to their numerous advantages [4]. The primary chemical components of plants, present in leaves, fruits, flowers, seeds, and occasionally even the entire herb, are called phytochemicals [5, 6]. Terpenoids, flavonoids, glycosides, phytosterols, saponins, carotenoids, alkaloids, aromatic acids, protease inhibitors, essential oils, and organic acids are the main groups of phytoconstituents (PCs) [7, 8]. They can diagnose, treat, and ultimately eradicate all chronic and degenerative diseases affecting human beings. The metabolites also offer defensive mechanisms (direct or indirect) against infections or hazardous illnesses, including antibacterial, anthelmintic, anticarcinogenic, anti-inflammatory, antigenotoxic, antimutagenic, antioxidative and antiproliferative [9,10,11]. The traditional plant has distinct pharmacological effects on the human body [12]. As a result, the evaluation concentrated on addressing the demands of society to determine the effectiveness of traditional treatments. The review aims to highlight the specifics of pharmacological activities along with in vitro and in vivo research of medicinal herb gossypin (GOS) using previous studies.

Overview of flavonoids

Cereals, fruits, nuts, herbs, vegetables, stems, flowers, as well as seeds are the most common sources of flavonoids, which are secondary metabolites [13]. The therapeutic efficacy and biological activity of these parts of plants are due to the PCs contained in them. Ten thousand flavonoids have been found and derived so far [13, 14]. Most flavonoids are commonly used as pharmaceuticals such as anthocyanidin and proanthocyanidin, isoflavone, anthocyanins, and gossypin [15]. The potential health advantages offered by the antioxidant capabilities of these polyphenols have sparked recent interest in these substances. To function as antioxidants, hydroxyl groups either bind metal ions or scavenge free radicals [16]. Flavonoids are thought to be dietary components with health-promoting properties. Also, the human body's defence-enhancing enzyme pathways can be activated by flavonoids [17]. Many plant species contain flavonoids, including chamomile, ginkgo biloba, hibiscus, and others (Fig. 1). Gossypins present in several plant species with a variety of biological functions because of its structural makeup [18]. It has been demonstrated to inhibit carcinogenesis, angiogenesis, and other processes. Gossypin thus receives much interest from researchers and scholars [19].

Fig. 1
figure 1

Basic flavonoid structure and their various types (Own creation)

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Structure and pharmaceutical importance of gossypin

Gossypins [2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4-oxo-4H-chromen-8-yl b-D-gluco-pyranoside] (Fig. 2) with a molecular formula (C21H20O13), a flavanol glucoside [20], are primarily found in flowers and roots of numerous hibiscus species, including H. esculentus, H.vitifolius, and G. indicum [21, 22] belonging to the "Malvaceae" family. Gossypin is like a gossypetin in terms of function [23]. It indicates physical properties including yellow crystalline solid powder, high melting point (229–230 °C), and markedly soluble in water. The existence of the glucose moiety makes the compound more soluble in water and less soluble in alcohol and other solvents [24]. Also, it is more stable than other phytoconstituents due to structural arrangements.

Fig. 2
figure 2

Basic structure of gossypin (Own creation)

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Pharmaceutical importance of gossypin

There are between 50,000 and 80,000 flowering plant species used for medicinal purposes worldwide. These herbs are supplemental or alternative medicine. For the development of new drugs, studies on these medicinal plants that include pharmacological and toxicological assessments are crucial globally. Since there are many different types of plants in India, there is a significant chance that their economic value can be maximized by developing technologies for their cultivation and processing [25, 26]. According to statistics, there are 18,000 species of higher plants in India with various phytogeological and ecological zones including Himalayas region, Karnataka, Maharashtra, Tamil Nadu, etc., of which around one-third are essential for health care and the economy [27]. However, less emphasis on therapeutic benefit of cotton metabolites containing rich oil and protein, which has medicinal value, might lead to the new way for a more thorough application of cotton products [28]. This is partially because of extensive interest in cotton as an economically viable crop for vegetable oil, feedstuff, and textile fibre. Gossypin is used in various fields, including those related to chemicals, medicine, and others (Fig. 3). As it can prevent cell proliferation, gossypin is employed in the pharmaceutical sector to develop the anticancer medications. Gossypin is a natural pigment used in the chemical industry as a colourant in soaps, cosmetics, as well as dyes; another uses are insecticide and antioxidant. Gossypol, gossypetin, gossypin, and gossypose are a few examples of the many metabolites or defensive substances produced by cotton plants [29, 30]. Gossypin can also be employed as an ether sizing agent belonging to the technical domains of preparing sizing agents [31]. Compared to the parent compound, Nair demonstrated that gossypin nanoparticle formulation successfully halted colony formation and growth in vitro. Gossypin may limit the proliferation and invasion of tumour cells and vascular permeability induced by VEGF and tumour neovascularization, causing cell cycle arrest [32]. Additionally, the gossypin has physical characteristics like marked solubility, increased bioavailability, and long-term effectiveness [33]. Thus, this phenomenon can be used in different gossypin formulations. NMR spectra by GIAO approximation revealed GOS-SWCNT structure, which appears the number of active sites in GOS-SWCNTs that have the most activity at indicated model proved by Shabanzadeh. This compound offers an atomistic examination of the GOS–SWCNT method and its use in ongoing pharmacological research [34]. Overall, gossypin and its derivatives perform vital economic part in the development of the pharmaceutical domain.

Fig. 3
figure 3

Segments of gossypin in the pharmaceutical industry (Own creation)

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Proven pharmacological activities of gossypin

Gossypin has attracted a lot of attention from academics and researchers because it not only has strong pharmacological effects but also has minimum adverse effects and easy preparation. The purpose of this part is to give a theoretical foundation for the clinical use of gossypin by briefly describing the pharmacological effects (Fig. 4) and mechanism of the drug [35] (Table 1).

Fig. 4
figure 4

Gossypin uses in variety of diseases (Own creation)

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Table 1 Gossypin activities along with study models
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Limitations of gossypin and solutions to overcome

Folklore systems originated in ancient times and are still in use today. According to Shrikumar, Complementary and Alternative Medicine (CAM) systems are a miracle for herbal and conventional medicine [36]. Moreover, certain factors constrained the usage of gossypin are as follows:

  • Gossypin is considerably more soluble in water and less in anhydrous organic solvents. It is challenging to obtain it completely free of mineral matter due to this property [37].

  • Another obstacle to extracting these compounds is that the flavonoids are typically labile, subjecting them to significant levels of chemical structure degradation or alteration and subsequent activity loss during purification [38].

  • Isolation and separation of gossypin from plant species are somewhat difficult as it was observed that very few ionic compounds were identified. Awouafack noted more moderately polar polyphenols, including certain terpenoids, steroidal chemicals, and gossypin [39].

  • Gossypin-powdered extract must be stored and handled carefully because it is hygroscopic and incompatible with strong oxidizers.

  • For these herbal bioactive, potential side effects include skin, eye, and respiratory irritation [40].

Solutions to overcome these issues

By increasing solubility, bioavailability, stability, also bioactivities of phytochemicals, nanotechnology has the potential to help overcome these obstacles [41]. The proniosomal drug delivery strategy, according to Jampala and colleagues, can improve the flow into the skin and produce the optimal sustainability effect of GOS. Considering this, using proniosomal gel to deliver gossypin topically for managing melanoma treatment could be useful [42]. Additionally, the liposomal-GOS formulation provides mice prevention from PTZ kindling. Liposomal-GOS treatment dramatically slowed the advancement of kindling in mice, making it an excellent candidate to manage the oxidative stress that occurs during epilepsy as well as the development of seizures [43].

Gossypin is more stable than most other naturally occurring chemicals owing to the existence of the -OH group in their structure, which stabilizes the molecule and prevents it from interacting with other substances. The methods, including high-performance liquid chromatography (HPLC), ion-exchange column chromatography, mass spectroscopy (MS), nuclear magnetic resonance (H1NMR), liquid chromatography-mass spectroscopy (LC–MS), high-performance thin layer chromatography (HPTLC), can be suitable techniques used to isolate and study the chemical composition of gossypin [44]. The low extraction yield of flavonoids produced by the existing conventional separation and purification procedures typically not able to justify the greater cost of extraction. The extraction yield of flavonoids could be increased by optimizing the conditions using response surface methodology over these conventional techniques. Diverse tactics are used to overcome these restrictions [45, 46].

In vitro and in vivo investigation of gossypin

In vitro studies of gossypin produced from Hibiscus species were carried out using cell lines or assays to determine the bioactivities. The description of the studies is shown in Table 2.

Table 2 In vitro studies of gossypin
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Gossypin’s in vivo studies

This research examined the bioactivities of the phytochemical using animal models. The description of studies is shown in Table 3.

Table 3 In vivo studies of gossypin
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Patents filed on gossypin

Filing and approving patents provide conclusive evidence of an item's commercial interest. In this regard, the researcher has received a few patents for their inventive work and study on gossypin PCs. The patent gives exclusive rights to innovation, which also prevents others from misusing it. A few of the patents, which are granted, are discussed in Table 4.

Table 4 Patents filed on gossypin
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Market analysis of gossypin

The gossypin market analysis provides information on market size, growth rate, segmentation, and a comparison of factors or challenges that could impact the market's future. Because of the increased need of herbal products, especially in nutraceutical and pharmaceutical industries, the GOS market is now expanding. Gossypin applications are becoming more varied, spanning from skincare to cancer treatment, further boosting the drug's market growth [47]. The market still has difficulties due to low extraction yields and a scarcity of raw materials. To optimize the potential of gossypin, it is crucial for key stakeholders and industry professionals to examine creative solutions to these problems. Gossypin is used in a variety of industries, including those related to chemicals, medicine, and others. Due to its capacity to impede cell proliferation, gossypin is utilized in the pharmaceutical sector in the development of anticancer medications. Gossypin is a natural pigment used in the chemical industry to colour cosmetics, soaps, and dyes. Gossypin can also be used as an insecticide and antioxidant, among other things. The market for gossypin has expanded owing to its variety of applications [48]. The areas that notably covered gossypin market are:

  • North America

  • Asia Pacific

  • Europe

  • Middle East and Africa

  • Latin America (Fig. 5).

Fig. 5
figure 5

(Source: Internet + Own) [50]

World distribution of gossypin

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Market players (company) in the gossypin

Gossypin presents in cotton plants with possible medical benefits. Some of the major participants in the gossypin market include Ambeed, BioCrickBio Tech, Baoji Herbest Bio, Henan Tianfu Chemical, BiosynthBLD pharm, BioVision Inc, Molekula Group, BOC Sciences, Rarus, Carbosynth, and Watson (Fig. 6). These organizations can contribute to the expansion of the GOS market by diversifying their geographic reach and investing in R&D to find new and innovative therapeutic uses [49, 50].

Fig. 6
figure 6

(Source: Internet + Own) [50]

Analysis report of gossypin along with the key players

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Conclusion

Many of the drugs utilized in the modern medical system originated from natural sources. Furthermore, traditional medicines were the primary form of healthcare for most populations in Asia and Africa, e.g., China, Japan, South Korea, India, etc. Due to the perception that they have fewer adverse effects and greater effectiveness, herbal medications are utilized worldwide to cure various acute and chronic disorders. Gossypin, a bioflavonoid, is naturally derived from Hibiscus species belonging to the Malvaceae family. Due to their structural makeup, they own a wide spectrum of bioactivities. Further, they also utilized in textile, cosmetics, and nutraceutical industries. Some identified biological activities were proved using animal models, cell lines or assays, supporting the concept. Overall, this review presented a database for beneficial effects, current scenarios and market analysis of gossypin, which will be attention for researchers in the future.

Future perspectives

The herbs are supplemental or alternative medicine. For the development of new drugs, studies on these medicinal plants that include pharmacological and toxicological assessments are crucial globally. Still some research needs to be done to evaluate the efficiency of herbal plants. The significant obstacle is the lack of an animal model that accurately imitates the histologic and immunophenotypic features of pharmacological actions. Thus, randomized controlled clinical trials are required in future research for the systematic evaluation of such herbs in terms of efficacy and safety in humans. To enhance the effectiveness of the treatment, molecular targets that control several critical pathogenic variables can also be targeted. More investigations are required to advance herbs provided nano-cosmetics, nanotechnology to ensure that nano-scaled plant extract-loaded formulations continue to be the excellent and unique option in the upcoming era. Considering the enormous potential that plant-based medications must treat a wide range of illnesses, it is now possible to state that much more knowledge and experience are still needed in this field.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Abbreviations

PCs:

Phytoconstituents

GOS:

Gossypin

NMR:

Nuclear magnetic resonance

SWCNT:

Single-walled carbon nanotubes

Cdc25C:

Cell division cycle 25C

Chk1:

Checkpoint kinase 1

LDLR:

Low-density lipoprotein receptor

SD:

Sprague–Dawley

CAM:

Complementary and Alternative Medicine

PEG:

Polyethylene glycol

HPLC:

High-performance liquid chromatography

MS:

Mass spectroscopy

LC-MS:

Liquid chromatography-mass spectroscopy

HPTLC:

High-performance thin-layer chromatography

GPG:

Gossypin-loaded gels

SM:

Sulphur mustard

UV:

Ultraviolet

VEGF:

Vascular endothelial growth factor

GIAO:

Gauge-independent atomic orbital

HbA1c:

Glycated haemoglobin

COX-2:

Cyclooxygenase 2

DNA:

Deoxyribonucleic acid

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide

HSV:

Herpes simplex virus

BHT:

Butylated hydroxytoluene

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

GABA:

Gamma-aminobutyric acid

I/R:

Ischemia-reperfusion

HMG-CoA:

β-Hydroxy β-methylglutaryl-CoA

SOD:

Superoxide dismutase

GSH:

Glutathione

TNF-α:

Tumour necrosis factor alpha

NF-kB:

Nuclear factor kappa B

IL:

Interleukin

ISO:

Isoprenaline

PTZ:

Pentylenetetrazole

MDA:

Methylenedioxyamphetamine

RBC:

Red blood cell

NO:

Nitric oxide

R&D:

Research and Development

References

  1. Raju GS, Moghal MR, Dewan SMR, Amin MN, Billah M (2013) Characterization of phytoconstituents and evaluation of total phenolic content, anthelmintic, and antimicrobial activities of Solanum violaceum Ortega, Avicenna. J Phytomedicine 3(4):313–320

    Google Scholar 

  2. Salmerón-Manzano E, Garrido-Cardenas JA, Manzano-Agugliaro F (2020) Worldwide research trends on medicinal plants. Int J Environ Res Public Health 17(10):3376. https://doi.org/10.3390/ijerph17103376

    Article  PubMed  PubMed Central  Google Scholar 

  3. World Health Organization report (2022) https://www.who.int/news/item/25-03-2022-who-establishes-the-global-centre-for-traditional-medicine-in-india.

  4. Biotonical survey of India, https://scroll.in/article/954167/india-is-home-to-over-8000-species-of-medicinal-plants-and-theyre-increasingly-under-threat.

  5. Altemimi A, Lakhssassi N, Baharlouei A, Watson DG, Lightfoot DA (2017) Phytochemicals: extraction, Isolation, and identification of bioactive compounds from plant extracts. Plants Basel Switz 6(4):42. https://doi.org/10.3390/plants6040042

    Article  CAS  Google Scholar 

  6. Oz AT, Kafkas E (2017) Phytochemicals in fruits and vegetables. In: Superfood and functional food: an overview of their processing and utilization, V. Waisundara and N. Shiomi. Eds InTech 2017. https://doi.org/10.5772/66987

  7. Bhattachar S (2011) Natural antimutagens: a review. Res J Med Plant 5(2):116–126. https://doi.org/10.3923/rjmp.2011.116.126

    Article  CAS  Google Scholar 

  8. Agidew MG (2022) Phytochemical analysis of some selected traditional medicinal plants in Ethiopia. Bull Natl Res Cent 46(1):87. https://doi.org/10.1186/s42269-022-00770-8

    Article  Google Scholar 

  9. Velu G, Palanichamy V, Rajan AP (2018) Phytochemical and pharmacological importance of plant secondary metabolites in modern medicine in bioorganic phase in natural food: an overview. Roopan SM, Madhumitha G, Eds Cham: Springer, 135–156. https://doi.org/10.1007/978-3-319-74210-6_8.

  10. Bouguellid G (2020) Antimutagenic, antigenotoxic and antiproliferative activities of Fraxinus angustifolia Vahl. leaves and stem bark extracts and their phytochemical composition. PLOS ONE 15(4):e0230690. https://doi.org/10.1371/journal.pone.0230690.

  11. Swargiary A, Roy MK, Verma AK (2021) In vitro study of the antioxidant, antiproliferative, and anthelmintic properties of some medicinal plants of Kokrajhar district, India. J Parasit Dis 45(4):1123–1134. https://doi.org/10.1007/s12639-021-01410-0

    Article  PubMed  PubMed Central  Google Scholar 

  12. Naseem U, Muhammad Z, Farhat Ali K, Shazeb K (2014) A review on general introduction to medicinal plants, its phytochemicals and role of heavy metal and inorganic constituents. Life Sci 11(7):520–527

    Google Scholar 

  13. Dave Mehta S, Upadhyay S, Rai G (2022) Importance of flavonoid as secondary metabolites in flavonoid metabolism: recent advances and applications in crop breeding. IntechOpen 2022. https://doi.org/10.5772/intechopen.107462

  14. Gonçalves BMF, Cardoso DSP, Ferreira MJU (2020) Overcoming multidrug resistance: flavonoid and Terpenoid nitrogen-containing derivatives as ABC transporter modulators. Molecules 25(15):3364. https://doi.org/10.3390/molecules25153364

    Article  CAS  Google Scholar 

  15. Ullah A (2020) Important flavonoids and their role as a therapeutic agent. Molecules 25(22):5243. https://doi.org/10.3390/molecules25225243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013:162750. https://doi.org/10.1155/2013/162750

    Article  CAS  Google Scholar 

  17. Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5:e47. https://doi.org/10.1017/jns.2016.41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nix A, Paull C, Colgrave M (2017) Flavonoid profile of the cotton plant. Gossypium Hirsutum: Rev Plants 6(4):43. https://doi.org/10.3390/plants6040043

    Article  CAS  Google Scholar 

  19. Tungmunnithum D, Thongboonyou A, Pholboon A, Yangsabai A (2018) Flavonoids and other phenolic compounds from medicinal plants for pharmaceutical and medical aspects: an overview. Med Basel Switz 5(3):93. https://doi.org/10.3390/medicines5030093

    Article  CAS  Google Scholar 

  20. Wang L (2018) Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2. Phytother Res p ptr 6253. https://doi.org/10.1002/ptr.6253

  21. Prabhakaran D, Rajeshkanna A, Senthamilselvi MM, Solomon S (2019) In vitro antioxidant and anti-inflammatory activities of the flower extracts of Hibiscus vitifolius L. Eur J Med Plants 1–8. https://doi.org/10.9734/ejmp/2019/v29i430160

  22. Singh A (2017) Ethics in herbal medicine. Ethno leaflets 11:206–211

    Google Scholar 

  23. Khalaf SS, Shalaby OA, Hassan AR, El-Kherbetawy MK, Mehanna ET (2023) Acacia nilotica stem bark extract ameliorates obesity, hyperlipidemia, and insulin resistance in a rat model of high fat diet-induced obesity. J Tradit Complement Med 13(4):397–407. https://doi.org/10.1016/j.jtcme.2023.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chapano C (2003) Plants of the Chimanimani District National Herbarium and Botanic Garden, Zimbabwe. 32

  25. Karimah A (2021) A comprehensive review on natural fibers: technological and socio-economical aspects. Polymers 13(24):4280. https://doi.org/10.3390/polym13244280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kumar ChMS (2023) Solar energy: a promising renewable source for meeting energy demand in Indian agriculture applications. Sustain Energy Technol Assess 55:102905. https://doi.org/10.1016/j.seta.2022.102905

    Article  Google Scholar 

  27. Revathi P (2013) Western Ghats of Tamil Nadu. J Medi Pla Res 7(28):2083–2097

    Google Scholar 

  28. Huang J, Chen X (2022) New function of gossypol, a natural product of cotton. J Cotton Res 5(1):28. https://doi.org/10.1186/s42397-022-00135-6

    Article  CAS  Google Scholar 

  29. Tanyeli̇ A, Eraslan E, Güler MC, Kurt N, Akaras N (2019) Gossypin Sıçanlarda Böbrek İskemi- Reperfüzyon Hasarına Karşı Korur. Kafkas Univ Vet Fak Derg 2019. https://doi.org/10.9775/kvfd.2019.22396

  30. Tian X (2018) Characterization of gossypol biosynthetic pathway. Proc Natl Acad Sci 115:23. https://doi.org/10.1073/pnas.1805085115

    Article  CAS  Google Scholar 

  31. A kind of preparation method of gossypin ether sizing agent. (2016) https://patents.google.com/patent/CN106120336A/en?q=(gossypin)&oq=gossypin

  32. Nair H, Veerapaneni P, Sophie D, Kirma N, Perla R, Tekmal R (2009) Nano-gossypin, a novel cdk2/VEGF inhibitor formulation against breast cancer. Cancer Res 69(2):3080. https://doi.org/10.1158/0008-5472.SABCS-3080

    Article  Google Scholar 

  33. Bhardwaj JS (2020) Protective effects of gossypin in colchicine-induced cognitive dysfunction and oxidative damage in rats

  34. Shabanzadeh E, Monajjemi M (2015) A nano-biotechnology study of gossypin-CNT as a productive drug for the treatment of diabetes. J Comput Nano 12(11):4076–4086

    Article  CAS  Google Scholar 

  35. Song B (2023) Gossypin: a flavonoid with diverse pharmacological effects. Chem Biol Drug Des 101(1):131–137. https://doi.org/10.1111/cbdd.14152

    Article  CAS  PubMed  Google Scholar 

  36. Shrikumar S (2007) Approaches towards development and promotion of herbal drugs. Pharmacogn Rev 1(1)

  37. Rao KV, Seshadri TR (1946) Constitution of gossypin—Part I. Proc Indian Acad Sci - Sect A 24(4):375. https://doi.org/10.1007/BF03171074

    Article  Google Scholar 

  38. Amawi H, Ashby CR, Tiwari AK (2017) Cancer chemoprevention through dietary flavonoids: what’s limiting? Chin J Cancer 36(1):50. https://doi.org/10.1186/s40880-017-0217-4

    Article  PubMed  PubMed Central  Google Scholar 

  39. Awouafack MD, Tane P, Morita H (2017) Isolation and structure characterization of flavonoids. In: Flavonoids - from biosynthesis to human health. Justino GC, Ed InTech. https://doi.org/10.5772/67881

  40. Safety data sheet. https://www.biosynth.com/Files/MSDS/MH/11/MSDS_MH11045_5000_EN.pdf

  41. Jahangir MA (2022) Phytonutrients and technological development in formulations. J Pharm Res Sci Technol 6(1):38–66. https://doi.org/10.31531/jprst.1000159

    Article  Google Scholar 

  42. Rajkumar J, Radha GV, Ganapaty S (2021) Topical drug delivery of gossypin from proniosomal gel formulations: In Vitro efficacy against human melanoma cells. Int J Appl Pharm 144–152. https://doi.org/10.22159/ijap.2021v13i1.39609

  43. Nagpal D, Agarwal N, Katare D (2016) Evaluation of liposomal gossypin in animal models of epilepsy. Int J Pharm Pharm Sci 8(4)

  44. Ngere JB, Ebrahimi KH, Williams R, Pires E, Walsby-Tickle J, McCullagh JSO (2023) Ion-exchange chromatography coupled to mass spectrometry in life science, environmental, and medical research. Anal Chem 95(1):152–166. https://doi.org/10.1021/acs.analchem.2c04298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang L, Cao YL, Jiang JG, Lin QS, Chen J, Zhu L (2010) Response surface optimization of ultrasound-assisted flavonoids extraction from the flower of Citrus aurantium L. var. amara Engl: Other Techniques. J Sep Sci 33(9):1349–1355. https://doi.org/10.1002/jssc.200900776

  46. Liu Y, Wang H, Cai X (2015) Optimization of the extraction of total flavonoids from Scutellaria baicalensis Georgi using the response surface methodology. J Food Sci Technol 52(4):2336–2343. https://doi.org/10.1007/s13197-014-1275-0

    Article  CAS  PubMed  Google Scholar 

  47. Our report on Gossypin market with 9% CAGR, covers the following areas: market sizing, market forecast, market industry analysis (2023–2030), 2023, https://www.marketwatch.com/press-release/our-report-on-gossypin-market-with-9-cagr-covers-the-following-areas-market-sizing-market-forecast-market-industry-analysis-2023---2030-2023-04-04

  48. Technological Advancements and Regional Gossypin Market Size Report 2023–2030. (2023) https://www.marketwatch.com/press-release/technological-advancements-and-regional-gossypin-market-size-report-2023-2030-2023-04-12

  49. Global Gossypin Market 2023 by Manufacturers, Regions, Type and Application, Forecast To 2029. (2023) https://www.absolutereports.com/global-gossypin-market-22462505

  50. Hibiscus Flower Powder Market Size, Share & Trends Analysis Report by Nature (Organic, Conventional), by Application (Food & Beverages, Pharmaceuticals, Personal Care & Cosmetics), by region, and Segment Forecasts, 2020 - 2027. (2023) https://www.grandviewresearch.com/industry-analysis/hibiscus-flower-powder-market.

  51. Venkatesan T, Sorimuthu Pillai S (2012) Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats: antidiabetic property of gossypin. J Diabetes 4(1):41–46. https://doi.org/10.1111/j.1753-0407.2011.00145.x

    Article  CAS  PubMed  Google Scholar 

  52. Saravanamuttu S, Sudarsanam D (2012) Antidiabetic plants and their active ingredients: a review. 3(10):3639–3650

  53. Mada SR, Metukuri MR, Burugula L, Reddanna P, Krishna DR (2009) Antiinflammatory and antinociceptive activities of gossypin and procumbentin - cyclooxygenase-2 (COX-2) inhibition studies: antiinflammatory activity of gossypin and procumbentin. Phytother Res 23(6):878–884. https://doi.org/10.1002/ptr.2727

    Article  CAS  PubMed  Google Scholar 

  54. Ferrándiz ML, Alcaraz MJ (1991) Anti-inflammatory activity and inhibition of arachidonic acid metabolism by flavonoids. Agents Actions 32(3–4):283–288. https://doi.org/10.1007/BF01980887

    Article  PubMed  Google Scholar 

  55. Ferrándiz ML, Nair AG, Alcaraz MJ (1990) Inhibition of sheep platelet arachidonate metabolism by flavonoids from Spanish and Indian medicinal herbs. Pharm 45(3):206–208

    Google Scholar 

  56. Babu BH, Jayram HN, Nair MG, Ajaikumar KB, Padikkala J (2003) Free radical scavenging, antitumor and anticarcinogenic activity of gossypin. J Exp Clin Cancer Res CR 22(4):581–589

    CAS  PubMed  Google Scholar 

  57. Shi L (2012) Gossypin Induces G2/M arrest in human malignant glioma U251 cells by the activation of Chk1/Cdc25C pathway. Cell Mol Neurobiol 32(2):289–296. https://doi.org/10.1007/s10571-011-9760-8

    Article  CAS  PubMed  Google Scholar 

  58. Kunnumakkara AB (2007) Gossypin, a pentahydroxy glucosyl flavone, inhibits the transforming growth factor beta-activated kinase-1-mediated NF-κB activation pathway, leading to potentiation of apoptosis, suppression of invasion, and abrogation of osteoclastogenesis. Blood 109(12):5112–5121. https://doi.org/10.1182/blood-2007-01-067256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Viswanathan S, Thirugnana Sambantham P, Reddy K, Kameswaran L (1984) Gossypin-induced analgesia in mice. Eur J Pharmacol 98(2):289–291. https://doi.org/10.1016/0014-2999(84)90604-6

    Article  CAS  PubMed  Google Scholar 

  60. Ganapaty S, Chandrashekhar VM, Narsu ML (2010) Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model. Indian J Biochem Biophys 47:2010

    Google Scholar 

  61. Lee JH, Kim YS, Lee CK, Lee HK, Han SS (1999) Antiviral activity of some flavonoids on herpes simplex viruses. Korean J Pharmaco 30(1):34–39

    CAS  Google Scholar 

  62. Zhang Y (2022) Cotton flower metabolites inhibit SARS-CoV-2 main protease. FEBS Open Bio 12(10):1886–1895. https://doi.org/10.1002/2211-5463.13477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ganapaty S, Chandrashekhar V, Chitme H, Ml N (2007) Free radical scavenging activity of gossypin and nevadensin: an in-vitro evaluation. Indian J Pharmacol 39(6):281. https://doi.org/10.4103/0253-7613.39147

    Article  CAS  Google Scholar 

  64. Chandrashekhar V, Ganapaty S, Ramkishan A, Narsu MI (2013) Neuroprotective activity of gossypin from Hibiscus vitifolius against global cerebral ischemia model in rats. Indian J Pharmacol 45(6):575. https://doi.org/10.4103/0253-7613.121367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rasilingam D, Duraisamy S, Subramanian R (2008) Anticonvulsant activity of bioflavonoid gossypin. Bangladesh J Pharmacol 4(1):51–54. https://doi.org/10.3329/bjp.v4i1.1081

    Article  Google Scholar 

  66. Lu N, Li Y, Qin H, Zhang X, Sun C (2008) Gossypin up-regulates LDL receptor through activation of ERK pathway: a signaling mechanism for the hypocholesterolemic effect. J Agric Food Chem 56(23):11526–11532. https://doi.org/10.1021/jf802607x

    Article  CAS  PubMed  Google Scholar 

  67. Cinar I (2022) In vivo and in vitro cardioprotective effect of gossypin against isoproterenol-induced myocardial infarction injury. Cardiovasc Toxicol 22(1):52–62. https://doi.org/10.1007/s12012-021-09698-3

    Article  CAS  PubMed  Google Scholar 

  68. Cheng G (2022) Cardioprotective effect of gossypin against myocardial ischemic/reperfusion in rats via alteration of oxidative stress, inflammation and gut microbiota. J Inflamm Res 15:1637–1651. https://doi.org/10.2147/JIR.S348883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Gautam P, Flora SJS (2010) Oral supplementation of gossypin during lead exposure protects alteration in heme synthesis pathway and brain oxidative stress in rats. Nutrition 26(5):563–570. https://doi.org/10.1016/j.nut.2009.06.008

    Article  CAS  PubMed  Google Scholar 

  70. Kim KY (2008) (−)-epigallocatechin gallate inhibits the pacemaker activity of interstitial cells of cajal of mouse small intestine. Korean J Physiol Pharmacol Off J Korean 12(3):111–115. https://doi.org/10.4196/kjpp.2008.12.3.111

  71. Viswanathan S, Thirugnana Sambantham P, Bapna JS, Kameswaran L (1984) Flavonoid-induced delay in the small intestinal transit: possible mechanism of action. Arch Int Pharmacodyn Ther 270(1):151–157

    CAS  PubMed  Google Scholar 

  72. Alam MA, Al-Jenoobi FI, Al-mohizea AM (2012) Everted gut sac model as a tool in pharmaceutical research: limitations and applications. J Pharm Pharmacol 64(3):326–336. https://doi.org/10.1111/j.2042-7158.2011.01391.x

    Article  CAS  PubMed  Google Scholar 

  73. Vijayaraghavan R, Sugendran K, Pant SC, Husain K, Malhotra RC (1991) Dermal intoxication of mice with bis(2-chloroethyl)sulphide and the protective effect of flavonoids. Toxicology 69(1):35–42. https://doi.org/10.1016/0300-483X(91)90151-P

    Article  CAS  PubMed  Google Scholar 

  74. Vijayaraghavan R, Gautam A, Sharma M, Satish H, Pant S, Ganesan K (2008) Comparative evaluation of some flavonoids and tocopherol acetate against the systemic toxicity induced by sulphur mustard. Indian J Pharmacol 40(3):114. https://doi.org/10.4103/0253-7613.42304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Gautam A, Vijayaraghavan R (2007) Prophylactic effect of gossypin against percutaneously administered sulfur mustard. Biomed Environ Sci 20:250–259

    CAS  PubMed  Google Scholar 

  76. Yoon I, Lee KH, Cho J (2004) Gossypin protects primary cultured rat cortical cells from oxidative stress- and β-amyloid-lnduced toxicity. Arch Pharm Res 27(4):454–459. https://doi.org/10.1007/BF02980089

    Article  CAS  PubMed  Google Scholar 

  77. Añón MT, Ubeda A, Alcaraz MJ (1992) Protective effects of phenolic compounds on CCl4-induced toxicity in isolated rat hepatocytes. Z Für Naturforschung C 47(3–4):275–279. https://doi.org/10.1515/znc-1992-3-417

    Article  Google Scholar 

  78. KardeÅŸ S (2016) Neuroprotective effect of Gossypin on glutamate-induced excitotoxic neuronal death in SH-SY5Y cell line. Toxicol Lett 258:S286. https://doi.org/10.1016/j.toxlet.2016.06.1997

    Article  Google Scholar 

  79. Bhaskaran S (2013) Gossypin as a novel selective dual inhibitor of v-raf murine sarcoma viral oncogene homolog B1 and cyclin-dependent kinase 4 for melanoma. Mol Cancer Ther 12(4):361–372. https://doi.org/10.1158/1535-7163.MCT-12-0965

    Article  CAS  PubMed  Google Scholar 

  80. Thamizhiniyan V, Vijayaraghavan K, Subramanian SP (2012) Gossypin, a flavonol glucoside protects pancreatic beta-cells from glucotoxicity in streptozotocin-induced experimental diabetes in rats. Biomed Prev Nutr 2(4):239–245. https://doi.org/10.1016/j.bionut.2012.07.002

    Article  Google Scholar 

  81. Yildiz K, Turalioglu MF, Tahiroglu V, Boy F, Yigit S (2021) Gossypin’in Fare Mekano-Biyoregülatör Modeli Deneysel Femur Kırıklarında Kırık İyileşmesi Üzerine Etkileri. Kafkas Univ Vet Fak Derg 2021. https://doi.org/10.9775/kvfd.2021.25516.

  82. Marc Winnefeld Sabine Hagemann Jörn Söhle Elke Grönniger Torsten Schläger Katrin Schmidt, Use of gossypetin and/or gossypin against skin aging. (2016) https://patents.google.com/patent/WO2016034400A1/en?q=(gossypin)&oq=gossypin

  83. The preparation method of the super thin fabric face of a kind of water and oil repellant. (2016) https://patents.google.com/patent/CN102633249B/en?q=(gossypin)&oq=gossypin

  84. Method for rapidly preparing carbon microspheres by using cotton cellulose. (2014) https://patents.google.com/patent/CN102633249B/en?q=(GOssypin)&oq=GOssypin

  85. A kind of medical dressing hydrogel compound fabric and its preparation method and application. (2018) https://patents.google.com/patent/CN105228658B/en?q=(gossypin)&oq=gossypin

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  1. Amrutvahini College of Pharmacy, Sangamner, Ahmednagar, Maharashtra, 422608, India

    Gayatri Jejurkar & Machindra Chavan

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GJ contributed to the design of the study; GJ and MC collected the samples; GJ and MC performed the experiments and analysis the data; GJ and MC drafted the paper; all authors read and approved the final manuscript.

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Jejurkar, G., Chavan, M. Therapeutic benefits of gossypin as an emerging phytoconstituents of Hibiscus spp.: a critical review. Futur J Pharm Sci 9, 95 (2023). https://doi.org/10.1186/s43094-023-00547-4

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