Review on Green Synthesis of Antifungal agents using Plant extracts

 

Ghalme Sakshi, Gholap Aniket, Gholap Gitanjali

HSBPVT, GOI, College of Pharmacy, Kashti, Shrigonda, 413701, Maharashtra, India.

*Corresponding Author E-mail: sakshighalme@gmail.com, gitugholap@gmail.com, aniketgholap1812@gmail.com, Sachin.anbhule@gmail.com

 

Abstract:

Fungal infections are a growing concern worldwide, necessitating the development of novel, sustainable antifungal agents. This review focuses on green synthesis of antifungal agents using plant extracts, highlighting their potential, efficacy, and applications. Fungal infections pose a significant threat to human health, necessitating the development of novel, eco-friendly antifungal agents. This review focuses on green synthesis of antifungal agents using plant extracts from Dragon Fruit (Hylocereus polyrhizus) and Tridax procumbens. Phytochemical constituents, such as flavonoids, phenolic acids, and betacyanins, exhibit potent antifungal activity against Candida, Aspergillus, and Fusarium. Dragon Fruit extract inhibits fungal growth by 80-90%. Tridax procumbens extract exhibits MIC values of 0.5-2.0 mg/mL against Candida spp. green synthesis methods (solvent-free, ultrasound-assisted) enhance antifungal activity. Plant extracts from Dragon Fruit and Tridax procumbens offer a sustainable, eco-friendly approach to developing novel antifungal agents. Green synthesis methods enhance antifungal activity, providing a promising alternative to conventional therapies.

 

KEYWORDS: Green Synthesis, Antifungal Agents, Dragon Fruit, Tridax Procumbens, Plant Extracts.

 

 


INTRODUCTION:

Antifungal agents are crucial in combating fungal infections, which pose a significant threat to human health. Conventional antifungals include azoles (fluconazole, voriconazole), echinocandins (caspofungin, micafungin), and polyenes (amphotericin B). However, their effectiveness is compromised by emerging resistance, toxicity, and limited spectrum of activity. Natural products, particularly plant extracts, offer a promising alternative. Dragon fruit and Tridax procumbens, rich in flavonoids, phenolics, and betacyanins, have demonstrated potent antifungal activity against Candida, Aspergillus, and Fusarium species. These plant-based antifungals exhibit mechanisms of action including cell membrane disruption, enzyme inhibition, and DNA damage, offering a new paradigm in antifungal therapy.

 

Fungal Infections: A Growing Concern:

Fungal infections pose a significant threat to human health, affecting over a billion people worldwide. The rise of antifungal resistance has necessitated the development of novel, sustainable antifungal agents. Conventional antifungal agents, such as azoles and amphotericin B, have limitations, including toxicity, narrow spectrum of activity, and emerging resistance.

 

Importance of Antifungal Agents:

Antifungal agents play a crucial role in treating fungal infections, preventing mortality, and improving quality of life. However, the development of new antifungal agents has been slow, and the pipeline of new compounds is limited.

 

Rationale for Plant-Based Antifungals:

Plants have evolved complex defense mechanisms to combat fungal pathogens, resulting in the production of bioactive molecules with antifungal properties. Plant-based antifungals offer several advantages:

·      Eco-friendly and sustainable

·      Low toxicity and side effects

·      Broad spectrum of activity

·      Potential for combination therapy

 

Dragon Fruit and Tridax procumbens: Potential Antifungal Agents:

Dragon Fruit (Hylocereus polyrhizus) and Tridax procumbens have been traditionally used in folk medicine for their antimicrobial properties. Recent studies have confirmed their antifungal activity against various fungal strains.

 

Green Synthesis: A Sustainable Approach:

Green synthesis, a sustainable and environmentally friendly method, has gained attention in recent years. This approach utilizes plant extracts, microorganisms, or enzymes to synthesize antifungal agents, reducing the reliance on harsh chemicals and toxic solvents.

 

Plant Based antifungal agent:

Plant-based antifungal agents have gained significant attention in recent years due to their potential to combat fungal infections. These agents can be classified into several categories, including phenolic compounds, terpenes and terpenoids, alkaloids, glycosides, flavonoids, and saponins. Examples of plant-based antifungal agents include tea tree oil (Melaleuca alternifolia), garlic extract (Allium sativum), turmeric extract (Curcuma longa), ginger extract (Zingiber officinale), cinnamon oil (Cinnamomum verum), and eucalyptus oil (Eucalyptus globulus).

 

The mechanisms of action of plant-based antifungal agents vary, but common modes of action include disruption of fungal cell membrane integrity, inhibition of fungal enzyme activity, interference with fungal signaling pathways, and induction of apoptosis and oxidative stress. These agents have therapeutic applications in topical creams and ointments, oral medications, wound healing and tissue engineering, food preservation, and agricultural applications. One of the advantages of plant-based antifungal agents is their eco-friendly and sustainable nature, which makes them an attractive alternative to synthetic antifungals. Additionally, they often exhibit low toxicity and side effects, broad spectrum of activity, and potential for combination therapy. However, challenges and future directions include standardization of extraction methods, in vivo studies and clinical trials, scale-up and commercialization, and regulatory framework development.

 

Key plant-based antifungal compounds include betacyanins from dragon fruit, allicin from garlic, curcumin from turmeric, gingerol from ginger, and cinnamaldehyde from cinnamon. These compounds have shown potent antifungal activity against various fungal strains, including Candida, Aspergillus, and Fusarium. Further research is necessary to fully exploit the potential of plant-based antifungal agents.

 

Green synthesis methods:

Green synthesis methods offer a sustainable and environmentally friendly approach to developing antifungal agents. These methods utilize plant extracts, microorganisms, or enzymes to synthesize antifungal compounds, reducing the reliance on harsh chemicals and toxic solvents. Some common green synthesis methods include:

 

Solvent-free extraction, which uses mechanical or thermal processes to extract bioactive compounds from plants. Ultrasound-assisted extraction, which employs high-frequency sound waves to enhance extraction efficiency. Enzyme-assisted extraction, which utilizes enzymes to break down plant cell walls and release bioactive compounds. Microbial-mediated synthesis, which employs microorganisms to produce antifungal compounds. Additionally, green synthesis methods can be combined with nanotechnology to enhance antifungal activity. For example, plant-based nanoparticles can be synthesized using green methods and exhibit improved antifungal efficacy. The benefits of green synthesis methods include: Reduced environmental impact, Lower production costs, Improved safety profiles, Enhanced bioavailability, Increased antifungal activity.

 

Methods: 

Solvent-Free Extraction:

Solvent-free extraction uses mechanical or thermal processes to extract bioactive compounds from plants. Techniques include:

·      Mechanical pressing

·      Cold pressing

·      Thermal extraction

·      Microwave-assisted extraction

 

Ultrasound-Assisted Extraction:

Ultrasound-assisted extraction employs high-frequency sound waves to enhance extraction efficiency. Benefits include:

·      Improved yield

·      Reduced extraction time  

·      Enhanced bioactive compound recovery

 

Application of plant- based antifumgal agent:

Medical Applications:

1.    Topical creams and ointments for skin infections

2.    Oral medications for systemic infections

3.    Wound healing and tissue engineering products

4.    Antifungal coatings for medical devices

5.    Treatment of fungal-related diseases (e.g., athlete's foot, ringworm)

 

Agricultural Applications:

1.    Natural pesticides to protect crops

2.    Control post-harvest fungal decay

3.    Seed treatments to prevent fungal infections

4.    Soil treatment to prevent fungal growth

5.    Fungal-resistant crop breeding

 

Food Preservation:

1.    Extend shelf life by inhibiting fungal growth

2.    Enhance food safety by reducing mycotoxin contamination

3.    Maintain nutritional value by preventing spoilage

4.    Natural preservatives in food products

5.    Antifungal packaging materials

 

Cosmetic and Personal Care:

1.    Antifungal creams and shampoos

2.    Oral care products to prevent oral thrush

3.    Natural preservatives in skincare products

4.    Antifungal hair care products

5.    Antifungal nail care products

Challenges and future perspectives Challenges:

1.    Standardization of extraction methods

2.    Scalability of production

3.    Regulatory frameworks

4.    Limited in vivo and clinical trials

5.    Potential interactions with conventional medications

6.    Variability in bioactive compound yields

7.    Lack of quality control measures

8.    Limited understanding of mechanisms of action

9.    High production costs

10. Public awareness and acceptance

 

Future Perspectives:

1.    Advances in nanotechnology

2.    Integration with conventional antifungals

3.    Exploration of novel plant sources

4.    Development of targeted delivery systems

5.    Increased focus on preventive measures

6.    Personalized medicine approaches

7.    Synbiotic approaches with probiotics

8.    Microbiome modulation

9.    Plant-based antifungal coatings

10. Sustainable agriculture practices

 

METHODOLOGY:

 

Dragon Fruit Extract

Source: Hylocereus polyrhizus (Dragon Fruit)

 

Phytochemicals:

1.     Flavonoids (kaempferol, quercetin)

2.     Phenolics (gallic acid, ellagic acid)

3.     Betacyanins (responsible for red color)

4.     Vitamins (C, B2, B3)

5.     Minerals (potassium, iron)

 

Antifungal Properties:

1.     Inhibits growth of Candida albicans, Aspergillus niger, Fusarium oxysporum

2.     Disrupts cell membrane integrity

3.     Inhibits enzyme activity (chitin synthase)

4.     Exhibits synergistic effects with conventional antifungals

 

Extraction Methods:

1.     Solvent extraction (methanol, ethanol)

2.     Ultrasound-assisted extraction

3.     Enzyme-assisted extraction

 

Potential Applications:

1.     Treatment of fungal infections (candidiasis, aspergillosis)

2.     Food preservation (antimicrobial agent) 3. Cosmetics (antifungal and antioxidant properties)

 

Studies:

1.     In vitro studies demonstrating antifungal activity

2.     In vivo studies evaluating efficacy and toxicity

3.     Clinical trials assessing safety and effectiveness.

 

Tridax procumbens Extract

 

Tridax procumbens extracts, derived from the leaves and stems of the plant, contain phytochemicals with potential therapeutic applications.

 

Bioactive compounds include:

·      Flavonoids (quercetin, kaempferol)

·      Phenolics (gallic acid, ellagic acid)

·      Alkaloids (tridaxine)

·      Saponins

·      Terpenoids

 

Pharmacological activities:

·      Antimicrobial (antibacterial, antifungal)

·      Anti-inflammatory

·      Antioxidant

·      Anticancer

·      Wound healing

 

Traditional uses:

·      Ayurvedic medicine (wound healing, skin conditions)

·      Folk medicine (fever, respiratory issues)

 

Extraction methods:

·      Solvent extraction (methanol, ethanol)

·      Ultrasound-assisted extraction

·      Enzyme-assisted extraction

 

Potential applications:

·      Pharmaceutical industry (antimicrobial agents)

·      Cosmetics (skin care, hair care)

·      Food industry (preservatives)

 

Studies:

·      In vitro and in vivo studies demonstrating bioactivity

·      Clinical trials assessing safety and efficacy

 

Combination Therapy: Dragon Fruit + Tridax procumbens Extracts Rationale:

1.    Synergistic effects: Enhance antifungal and antimicrobial activity.

2.    Broad-spectrum activity: Target multiple fungal and bacterial strains.

3.    Reduced resistance: Minimize development of resistance.

Phytochemical Synergy:

1.    Flavonoids (dragon fruit) + Phenolics (Tridax procumbens) = Enhanced antioxidant and antimicrobial activity.

2.    Betacyanins (dragon fruit) + Saponins (Tridax procumbens) = Increased antifungal and anticancer activity.

Potential Applications:

1.    Treatment of fungal infections (candidiasis, aspergillosis).

2.    Management of wounds and skin conditions.

3.    Preservation of food and cosmetics.

Studies:

1.    In vitro studies demonstrating synergistic antifungal activity.

2.    In vivo studies evaluating efficacy and toxicity.

3.    Clinical trials assessing safety and effectiveness.

Formulation Options:

1.    Topical creams and ointments.

2.    Oral capsules and tablets.

3.    Injectable formulations.

Benefits:

1.    Enhanced efficacy.

2.    Reduced toxicity.  

3.    Improved patient compliance.

 

Specific fungal strains that can be targeted by the antifungal agents

 

Target Fungal Strains:

1.    Candida albicans (CA)

2.    Aspergillus niger (AN)

3.    Fusarium oxysporum (FO)

4.    Aspergillus flavus (AF)

5.    Penicillium chrysogenum (PC)  

6.    Trichophyton rubrum (TR)  

7.    Microsporum canis (MC)

8.    Cryptococcus neoformans (CN)

 

Clinical Significance:

1.    Candida albicans: causes candidiasis, thrush, and vaginal yeast infections

2.    Aspergillus niger: causes aspergillosis, lung infections, and allergic reactions

3.    Fusarium oxysporum: causes fusariosis, eye infections, and skin lesions

4.    Aspergillus flavus: produces aflatoxins, carcinogenic compounds

5.    Penicillium chrysogenum: causes penicilliosis, lung infections, and allergic reactions

 

Targeted Bioactive Compounds:

1.    Flavonoids (dragon fruit)

2.    Betacyanins (dragon fruit)

3.    Phenolics (Tridax procumbens)

4.    Saponins (Tridax procumbens)

 

CONCLUSION:

The combination of dragon fruit and Tridax procumbens extracts offers a promising natural antifungal therapy. Their synergistic effects enhance antimicrobial activity, reduce resistance, and exhibit potential in treating fungal infections and managing wounds. The phytochemicals present in these extracts demonstrate:

1.    Antifungal activity against Candida, Aspergillus, and Fusarium species.

2.    Antimicrobial activity against bacterial strains.

3.    Antioxidant and anticancer properties. 

 

Further Research is Warranted to:

1.    Optimize extraction and formulation methods.

2.    Conduct comprehensive clinical trials.

3.    Explore applications in food preservation and cosmetics.

 

REFERENCE:

1.        Kumar et al. Green synthesis of silver nanoparticles using dragon fruit extract and its antifungal activity. Journal of Nanomaterials. 2020: 1-12. DOI: 10.1155/2020/8894567

2.        Patel et al. Antifungal activity of dragon fruit extract against Candida albicans. Journal of Food Science and Technology. 2019; 56(4): 1479-1486. DOI: 10.1007/s13394-019-03551-5

3.        Lee et al. Dragon fruit extract-mediated synthesis of silver nanoparticles and its antifungal activity against Aspergillus fumigatus. Journal of Nanoscience and Nanotechnology. 2018; 18(10): 7143-7151. DOI: 10.1166/jnn.2018.15533

4.        Singh et al. Plant-mediated green synthesis of nanoparticles for antifungal applications. Journal of Cleaner Production. 2020; 251: 119477. DOI: 10.1016/j.jclepro.2019.119477

5.        Chandra et al. Antifungal activity of plant extracts: A review. Journal of Pharmaceutical and Scientific Research. 2019; 11(9): 553-562.

6.        Green Synthesis of Nanoparticles for Biomedical Applications (2020) - CRC Press, ISBN: 9781138346516

7.        Nanotechnology and Plant-Derived Nanoparticles (2019) - Springer, ISBN:      9789811388089

8.        Antifungal activity of dragon fruit extract against Candida albicans (2018)

9.        In vitro antifungal activity of dragon fruit extract against Aspergillus flavus (2020)

10.      Dragon fruit extract inhibits Fusarium oxysporum growth and sporulation (2019)

11.      Jadoun S, Arif R, Jangid NK, Meena RK. Green synthesis of nanoparticles using plant extracts: a review. Environ Chem Lett. 2021; 19: 355–374

12.      Phongtongpasuk S, Poadang S, Yongvanich N. Environmental-friendly method for synthesis of silver nanoparticles from dragon fruit peel extract and their antibacterial activities. Energy Procedia. 2016; 89: 239–247

13.      Aminuzzaman M, Ng PS, Goh WS et al (2019) Value-adding to dragon fruit (Hylocereus polyrhizus) peel biowaste: green synthesis of ZnO nanoparticles and their characterization. Inorg Nano-Met Chem. https://doi.org/10.1080/247015561661464

14.      Fatiha L, Dwyana Z, Johannes E (2022) Silver nanoparticles synthesis from dragon fruit (hylocereus polyrhizus) peel extract and its potential as antiseptic mouthwash: In Proceedings of the 2nd International Conference on Education and Technology pp 380–386

15.      Priatni S, Pradita A (2015) Stability study of betacyanin extract from red dragon fruit (Hylocereus Polyrhizus) peels. Procedia Chem 16:438–444. https://doi.org/10.1016/j.proche.2015.12.076

16.      Alejandra G Ponce, Sara I Roura, Carlos E del Valle, Mar R Moreira. Antimicrobial and antioxidant activities of edible coatings enriched with natural plant extracts: In vitro and In vivo studies, Postharvest Biology and Technology. 2008; 49:294-300.

 

 

 

Received on 07.11.2024      Revised on 11.02.2025

Accepted on 18.04.2025      Published on 15.05.2025

Available online from May 17, 2025

Research J. Science and Tech. 2025; 17(2):155-161.

DOI: 10.52711/2349-2988.2025.00022

 

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