A Review on Phytochemical and Pharmacological Insight into Artemisia Annua L. In Wound Healing

The biggest organ in the human body, the skin acts as a barrier to shield inside organs from UV rays and microbial invasion. Skin injuries are common, can cause significant bleeding, and can occasionally be fatal. Skin injuries, or wounds, are defined as flaws in the skin brought on by mechanical, thermal, and other traumas. Restoring the structure and functionality of the extracellular matrix (ECM) of the skin is the goal of the skin repair process, which typically consists of four steps: inflammation, migration, new tissue synthesis, and tissue remodeling [1].

Wounds that compromise the structural integrity of the skin can arise from a variety of causes, including burns, scalds, incisions, pressure sores, diabetic foot ulcers, and venous ulcers. These injuries undermine the skin's protective capabilities, heightening the likelihood of infections and prolonging the healing process. In recent years, phytochemicals have demonstrated significant promise in both preventing and treating microbial infections associated with wounds [2]. Phytochemicals, known for their antioxidant, antimicrobial, and wound healing characteristics, are essential in accelerating the healing process by encouraging clot formation, fighting infections, and aiding in tissue regeneration [3].

Medicinal plants that are abundant in polyphenols, especially phenolic compounds known for their astringent characteristics, have been recognized for their remarkable ability to promote wound healing[4].It is believed that components derived from medicinal plants are less harmful and exhibit fewer adverse effects in comparison to conventional therapeutic agents; thus, there is a growing and renewed interest in the utilization and implementation of medicinal plants in the wound healing process for both diabetic and non-diabetic conditions.

The difficulty in healing diabetic wounds is regarded as a significant health challenge for healthcare professionals worldwide, and this is associated with non-specific causes in certain instances; consequently, one of the treatment strategies involves the use of medicinal plants, especially in resource-limited environments[5].The growing demand and accessibility of medicinal products have necessitated the isolation and comprehension of the principles that govern their therapeutic activities and efficacy. For example, the stimulation of fibroblasts by plant extracts has been identified as one of the mechanisms through which medicinal plants promote the wound healing process[6].Extracts from medicinal plants have been recorded to stop bleeding from fresh wounds, inhibit microbial growth, and enhance the healing of wounds[7].Traditional herbal remedies have been emphasized as alternative treatments that are less prone to causing negative side effects, in contrast to chemically synthesized substances[8].

Artemisia annua L., commonly referred to as sweet wormwood, is a medicinal plant renowned for its potential therapeutic properties, particularly in the treatment of inflammatory diseases, cancer, ulcers, liver conditions, and cardiovascular diseases [9]. Artemisia annua L. is an annual herb that originates from Asia and other continents, and it has been utilized for both the treatment and prevention of fever, chills, and malaria in both traditional and modern medicine [.Artemisia annua L. is regarded as a promising element for use in wound healing applications. Besides the aforementioned uses (such as the treatment of malaria, among others), several studies have indicated that Artemisia species have been utilized in wound healing due to their antibacterial, antimicrobial, and anti-inflammatory properties[10].Artemisinin is recognized for its antibacterial, antifungal, antileishmanial, antioxidant, anticancer, and anti-inflammatory properties. Sesquiterpenoids, flavonoids, coumarins, lipoids, phenolics, purines, steroids, triterpenoids, aliphatics, and artemisinin are just a few of the numerous compounds that have been extracted from Artemisia annua L[11].In an effort to alleviate the burden of wounds, significant attention has been directed towards comprehending the physiology of healing and wound care, with a particular focus on innovative therapeutic strategies and the ongoing advancement of technologies for both acute and chronic wound management[12].

2. BIOLOGY OF WOUND HEALING:

A wound represents a physical disruption or damage to functional tissue, and its healing is a multifaceted process that includes four overlapping phases: hemostasis, inflammation, proliferation, and tissue remodeling. This coordinated sequence of biochemical and cellular events is essential for the repair of damaged tissues [13].

2.1 Hemostasis phase takes place immediately following an injury to cease bleeding and establish a provisional matrix. Vasoconstriction diminishes blood flow, while platelets adhere, aggregate, and release factors including ADP, serotonin, and thromboxane A?. Fibrin creates a stable clot that acts as a scaffold for inflammatory cells and fibroblasts. Platelet-derived growth factors (PDGF, TGF-β and VEGF) trigger the inflammatory and proliferative phases [14].

2.2 Inflammatory phase commences within a few hours and continues for 3 to 5 days. Neutrophils are the initial responders, tasked with eliminating debris and bacteria through phagocytosis. Subsequently, macrophages arrive, secreting cytokines and growth factors (such as VEGF and TGF-β) that facilitate angiogenesis, the migration of fibroblasts, and the shift to the proliferative phase. It is crucial to maintain controlled inflammation, as extended inflammation can hinder the healing process [15].

2.3 Proliferative phase which lasts from 4 to 21 days, is characterized by the proliferation of fibroblasts, deposition of collagen, angiogenesis, and the formation of granulation tissue.During this phase, keratinocytes migrate to cover the wound, and endothelial cells develop new capillaries. This stage is crucial for restoring tissue structure and setting the stage for remodeling [16].

2.4 Remodeling phase may extend from several weeks to months, during which collagen III is substituted with collagen I, thereby enhancing the strength of the tissue. Scar tissue develops, vascularity diminishes, and the wound reaches its peak tensile strength. Adequate remodeling is essential for both functional and aesthetic recovery [17].

3. BOTANICAL PROFILE, GEOGRAPHICAL DISTRIBUTION, AND TAXONOMY OF ARTEMISIA ANNUA

• 1. Taxonomical Classification
• Kingdom: Plantae
• Division: Magnoliophyta
• Class: Magnoliopsida
• Order: Asterales
• Family: Asteraceae
• Genus: Artemisia
• Species: Artemisia annua L.

Artemisia annua L. belongs to the genus Artemisia within the family Asteraceae, which comprises more than 500 species distributed worldwide.

3.2 Botanical Description

Artemisia annua is a Chinese herb that grows to a height of 70–160 cm, featuring extensive branching, sparse hair, and a strong aroma (Klayman, 1993). The stem is upright, displaying a violet-brown to brownish color, ribbed, and covered with small, closely spaced hairs.

Fig. 1: Artemisia Anuua L.

 The leaves measure 3–5 cm in length and 2–4 cm in width. The flowers located around the perimeter are pistillate, numbering 10–20, filamentous, and have punctate and pointed tips; the stigmas are narrow and obtuse, extending from the corolla tube. Additionally, the flowers are hermaphroditic, with a count of 10–30, cupped in shape, light in color, and contain narrowly linear anthers with long apical and short basal appendages [18].

3.3 Geographical Distribution

This plant is native to Eurasia, primarily from the temperate regions of Asia, including China and India, as well as certain locations in Europe and northern Africa. Currently, it is cultivated in various other regions across the globe, such as Europe, the Americas, and Australia. Typically, it thrives in temperate climates but can also be located in subtropical zones. The plant favors full sunlight and is frequently found at elevations ranging from 1,000 to 1,500 meters above sea level [19].

4. TRADITIONAL USES:  

1. Artemisia annua has been utilized for more than 2000 years as an antipyretic for malarial fever, tuberculosis, and in Traditional Chinese Medicine , for "fever induced by summer heat" as well as for "afternoon fever linked to yin deficiency."
2. A. annua is recognized as a treatment for bleeding wounds and hemorrhoids [20].
3. It is advised to utilize the plant for the treatment of tumors, to combat infections caused by protozoa from the genera Plasmodium, Acanthamoeba, Schistosoma, and Leishmania, to address viral diseases (such as AIDS and hepatitis B), and to manage bacterial infections [21].
4.  In Traditional Chinese Medicine, A. annua is also suggested for autoimmune disorders like systemic lupus erythematosus and rheumatoid arthritis [22].
5. Extracts from A. annua seeds can be employed in the treatment of eye conditions [23].

5. PHYTOCHEMICAL COMPONENTS:

•Sesquiterpenoids / Terpenoids: These are the primary compounds that are responsible for antimalarial, anticancer, and antiparasitic effects.

•Flavonoids: Compounds like quercetin, rutin, artemetin, and casticin display antioxidant, anti-inflammatory, antimicrobial, and anticancer characteristics.

•Phenolic Acids: This group includes caffeic acid, chlorogenic acid and other phenolic compounds that contribute to antioxidant and anti-inflammatory benefits.

•Coumarins: Scopoletin and scopolin are included, providing antimicrobial and anti-inflammatory properties.

•Glycosides: Steroidal glycosides have been recognized, which may play a role in various pharmacological effects.

•Fatty Acids: Both saturated and unsaturated fatty acids are present, with some exhibiting antibacterial properties [24].

6. PHARMACOLOGICAL PROPERTIES OF ARTEMISIA ANNUA:

• Antimalarial properties: A. annua serves as the primary source of artemisinin, a sesquiterpene lactone known for its strong efficacy against Plasmodium species, including those resistant to drugs [25].

• Antioxidant properties: Extracts from A. annua exhibit significant free radical scavenging capabilities and the ability to inhibit oxidative stress, primarily attributed to phenolic compounds and flavonoids.

• Antimicrobial properties: The plant demonstrates extensive antimicrobial effects against a variety of bacteria and fungi, positioning it as a potential treatment for microbial infections.

• Anti-inflammatory properties: Numerous studies indicate that extracts from A. annua can diminish inflammatory mediators such as nitric oxide and proinflammatory cytokines [26].

• Anticancer / Cytotoxic properties: Various components, including artemisinin and flavonoids, have been shown to inhibit growth and induce apoptosis in different cancer cell lines [27].

• Antiviral properties: Extracts have demonstrated antiviral and virucidal effects against pathogens like SARS-CoV-2 in controlled experimental conditions [28].

• Antiparasitic and broad-spectrum antimicrobial effects: Beyond malaria, A. annua extracts are effective against other parasites and microbial pathogens [29].

• Immunomodulatory and metabolic properties: The plant has been noted for its ability to modulate immune responses and display antidiabetic and bone-protective effects in experimental studies [30].

CONCLUSION

In conclusion, Artemisia annua L. is a valuable medicinal plant with strong potential in wound healing. It contains many beneficial natural compounds, especially Artemisinin, along with flavonoids and phenolic compounds that provide antioxidant, anti-inflammatory, and antimicrobial effects. These properties are important because proper wound healing requires control of infection, reduction of inflammation, and protection against oxidative damage. The plant’s ability to support fibroblast growth, collagen formation, and tissue repair suggests that it may help speed up the healing process in both normal and chronic wounds, including diabetic wounds. Its traditional use, combined with modern scientific findings, supports its therapeutic importance.

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