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Therapeutic benefits of gossypin as an emerging phytoconstituents of Hibiscus spp.: a critical review

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)

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)

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)

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)

Table 1 Gossypin activities along with study models

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

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

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

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

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

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

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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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Correspondence to Gayatri Jejurkar.

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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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