Herbal Foot Crack Sheet: A Comprehensive Review of Medicinal Plants for Wound Healing and Skin Repair

Table 1. Botanical Characteristics, Biological Source, Physicochemical Properties, Chemical Constituents, and Pharmacological Activities of Aloe vera (L.) Burm.F. ^[7–9]

7.1.2 Pharmacological Activities

Aloe vera exhibits a broad spectrum of pharmacological activities that contribute significantly to skin repair and wound management. It promotes wound healing by stimulating angiogenesis, collagen synthesis, fibroblast proliferation, and re-epithelialization, thereby accelerating tissue repair and wound closure. Acemannan, the principal bioactive polysaccharide, plays a pivotal role in modulating cellular responses involved in the healing process. ^[9,10] In addition, Aloe vera possesses potent anti-inflammatory activity by regulating inflammatory mediators and reducing the prolonged activation of pathways such as NF-κB, thereby limiting excessive inflammation and promoting effective healing. ^[10] Its antioxidant properties further protect damaged tissues by scavenging reactive oxygen species (ROS), reducing oxidative stress, and minimizing oxidative injury to skin cells during wound repair. ^[9,10]

Furthermore, Aloe vera exhibits antimicrobial activity against a wide range of bacteria and fungi, primarily due to the presence of phenolic compounds, anthraquinones, and saponins, which help protect damaged skin from microbial infection. ^[8,10] The mucopolysaccharides present in Aloe barbadensis gel possess excellent water-retaining properties that enhance skin hydration and are particularly beneficial in managing dry skin and cracked heels. ^[7,8] Additionally, Aloe vera demonstrates immunomodulatory activity by stimulating macrophage function and regulating immune mediators involved in tissue regeneration. Acemannan has been shown to enhance cytokine production and promote the release of macrophage-derived mediators that facilitate tissue repair and wound healing. ^[10]

7.1.3 Aloe Vera's Mechanism of Action

By controlling age-related pathways that take place throughout the inflammatory, antioxidant, immunological, and cellular repair responses, aloe vera speeds up wound healing. The main physiologically active polysaccharide in aloe vera, acemannan, stimulates immune cells and macrophages to multiply and boost cytokinergic activity during the early stages of recovery. ^[10]

Aloe vera has been shown to decrease protracted inflammatory reactions, boost keratinocyte migration, which promotes re-epithelialization and wound closure, and control high NF-B activity during inflammation.^[10]

Through direct interactions with reactive oxygen species (ROS) and the activation of Nrf2-dependent antioxidant gene expressions, acemannan and other polysaccharides exhibit antioxidant activity that maintains redox balance and protects against oxidative damage.^[10]

Acemannan may also start signaling pathways such as cyclin D1 and AKT/mTOR cell proliferation, granulation tissue creation, collagen abundance, and tissue regeneration. The robustness of the skin barrier and the antibacterial efficacy of anthraquinone derivatives and saponins would improve wound healing. ^{[10, 11]}

7.1.4 Uses of Aloe vera

Aloe vera is extensively used in pharmaceutical, cosmetic, and dermatological formulations owing to its moisturizing, wound-healing, anti-inflammatory, and skin-protective properties. It is widely incorporated into products for the treatment of cracked heels, wound healing, burn management, and skin hydration. In addition, Aloe vera is a common ingredient in anti-aging products, moisturizers, sunscreens, anti-acne preparations, hydrogel wound dressings, herbal foot crack sheets, and skin tissue engineering applications because of its ability to promote skin regeneration, maintain moisture balance, and enhance tissue repair. ^[7,9]

7.1.5 Processing of Aloe vera

The first step in processing aloe vera is gathering ripe, healthy leaves, usually between three and four years old. To get rid of dirt and surface impurities, the collected leaves are thoroughly cleaned with filtered water. To reduce the possibility of skin irritation, the yellow latex layer containing aloin is then carefully drained. The translucent interior gel is extracted once the latex is removed by peeling off the outer rind. After homogenizing the gel to achieve a consistent consistency, fibrous debris and other contaminants are removed by filtering it via membrane filters or muslin fabric. Preservatives like sodium benzoate or ascorbic acid may be added to increase product stability. The gel is freeze-dried or spray-dried when a powdered form is needed for medicinal formulations. Finally, the processed Aloe Vera gel or powder is stored in airtight, light-resistant containers under refrigerated conditions to maintain its stability and biological activity. ^[8]

7.1.6 Advantages in Herbal Foot Crack Sheet

Aloe vera offers several advantages that make it an ideal ingredient for the development of herbal foot crack sheets. Its excellent moisturizing properties help restore skin hydration and prevent excessive dryness, while its wound-healing activity accelerates tissue repair and promotes faster healing of heel fissures. Aloe vera also exhibits antimicrobial activity that helps prevent microbial infections and possesses anti-inflammatory properties that reduce inflammation and discomfort at the affected site. Furthermore, it stimulates collagen synthesis, thereby enhancing skin regeneration and improving the structural integrity of damaged tissue. Owing to its biocompatibility, non-toxic nature, and suitability for topical drug delivery, Aloe vera is considered a safe and effective component of herbal foot crack sheet formulations. Additionally, it improves skin elasticity, contributing to enhanced skin flexibility and reducing the likelihood of recurrent fissure formation. ^[9,10]

7.2 Centella Asiatica

Figure 3 Centella asiatica (Gotu kola)

Table 2. Botanical, Physicochemical, Phytochemical, and Pharmacological Profile of Centella Asiatica (L.) Urb. ^[11–13]

7.2.1 Introduction

Centella asiatica (L.) Urb., often known as gotu kola, Indian pennywort, or mandukaparni, is an edible perennial herbal plant belonging to the Apiaceae family. Numerous tropical and subtropical regions in Asia, Africa, Australia, and South America are home to it. The entire plant has long been utilized in Ayurvedic, Chinese, and other traditional medicines for its ability to heal wounds, prevent burns, cure ulcers, and treat skin and inflammatory conditions ^{[11, 12]}

Centella asiatica's ability to heal wounds is primarily attributed to its pentacyclic triterpenoid saponins, which include asiaticoside, madecassoside, asiatic acid, and madecassic acid. These saponins stimulate collagen synthesis, induce angiogenesis, initiate fibroblast proliferation, and modulate extracellular matrix remodeling. ^{[11, 13]}

Numerous wound healing, antioxidant, antibacterial, anti-inflammatory, and skin regeneration activities of CE have been demonstrated by recent pharmacological study. As a result, it has been extensively developed into topical creams, gels, hydrocolloid dressings, cosmetics, and herbal wound dressings. When used into herbal sheets for the treatment of cracked heels, CE has demonstrated the etiological effects of increased skin elasticity and reduced scar formation.^{[11, 13]}

7.2.2 Pharmacological Activities

Centella asiatica exhibits a wide range of pharmacological activities that contribute to its effectiveness in wound healing and skin regeneration. Its wound-healing activity is primarily attributed to triterpene saponins, particularly asiaticoside and madecassoside, which stimulate collagen secretion and fibroblast proliferation, promote granulation tissue formation, and accelerate tissue regeneration^{. [11, 13]} In addition, Centella asiatica possesses significant anti-inflammatory properties by regulating inflammatory mediators such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and cyclooxygenase enzymes, thereby reducing excessive inflammatory responses during the wound-healing process. ^[13] The plant also demonstrates potent antioxidant activity due to the presence of flavonoids and phenolic compounds, which scavenge reactive oxygen species (ROS), reduce oxidative stress, and protect skin cells from oxidative damage, thereby facilitating efficient tissue repair. ^{[12, 13]} Furthermore, extracts of Centella asiatica exhibit antibacterial and antifungal activities against several skin pathogens, which may help prevent secondary infections in damaged skin. ^[13] The plant also promotes angiogenesis by regulating vascular endothelial growth factor (VEGF), thereby improving blood supply, oxygenation, and nutrient delivery to regenerating tissues. ^[11] Additionally, Centella asiatica exerts anti-scarring effects by regulating collagen deposition and extracellular matrix remodeling, which enhances skin elasticity and minimizes excessive scar formation. ^{[11, 13]}

7.2.3 Centella Asiatica's Mechanism of Action

The triterpenoid components of Centella asiatica are primarily responsible for its ability to heal wounds. Asiaticoside and madecassoside, two tri-terpenoids found in Indian pennywort, are known to activate the TGF---/Smad pathway in fibroblasts, causing fibroblast proliferation, collagen biosynthesis, and granulation tissue development. ^{[11, 13]}

The TGF-/Smad signaling pathway stimulates myofibroblast development and ECM remodeling, both of which aid in tissue regeneration and wound contraction. Only tissue regeneration can be encouraged by normal TGF-/Smad pathway regulation; fibrosis results from over regulation. ^[11]

All phases of wound healing, including fibroblast proliferation, collagen synthesis, vascular formation, matrix remodeling, and anti-inflammatory action, are generally involved by C. Asiatica. ^{[11, 13]}

7.2.4 Uses of Centella Asiatica

Centella asiatica is widely utilized in pharmaceutical, cosmetic, and dermatological formulations owing to its diverse therapeutic properties. It is commonly used for wound healing, the treatment of cracked heels and foot fissures, burn management, scar reduction, skin rejuvenation, and anti-aging formulations. In addition, it is incorporated into products intended for the reduction of stretch marks, management of venous insufficiency, treatment of pressure ulcers, and diabetic wound care. Owing to its excellent wound-healing and skin-regenerative potential, Centella asiatica is also used in hydrogel wound dressings and herbal foot crack sheets. ^{[11, 13]}

7.2.5 Processing of Centella Asiatica

Centella asiatica is first processed by gathering healthy aerial parts during the flowering stage and then thoroughly cleaning it under running water. The plant material is then milled into a fine powder after being shade-dried till the moisture level is less than 10%. Hydroalcoholic (70% ethanol), methanolic, or aqueous solvents are used for extraction. Rotary evaporation is used to concentrate the resultant extract under low pressure after it has been filtered via Whatman filter paper or muslin cloth. The concentrated extract is then freeze-dried or spray-dried to produce a stable extract powder, which is then kept in cool, sealed, light-resistant containers to maintain its stability and bioactivity. ^[12]

7.2.6 Advantages in Herbal Foot Crack Sheet

Centella asiatica offers several advantages when incorporated into herbal foot crack sheets. It enhances wound healing by promoting collagen formation and tissue regeneration, reduces inflammation, and provides antioxidant protection against oxidative stress. In addition, it improves skin elasticity, helps prevent microbial complications through its antimicrobial activity, and is highly biocompatible, making it suitable for topical applications in the management of heel fissures and other skin wounds. ^{[11, 13]}

7.3 Calendula Officinalis

Figure 5 Calendula officinalis

Table 3. Botanical, Physicochemical, Phytochemical, and Pharmacological Profile of Calendula Officinalis L. ^[14–16]

7.3.1 Introduction

Pot marigold, or Calendula officinalis L., is a medicinal annual herb belonging to the Asteraceae family. Because of its medicinal, cosmetic, and pharmaceutical uses, this native of the Mediterranean basin has been grown in temperate climates all over the world. The main component of herbal medicine is the dried flower heads, which are traditionally used to heal wounds, burns, cuts, ulcers, dermatitis, eczema, and other inflammatory skin conditions. ^{[14, 15]}

Triterpenoids, flavonoids, carotenoids, phenolic acid, saponins, and essential oils are the primary bioactive components that contribute significantly to the pharmacological effects of has. The anti-inflammatory, antioxidant, antibacterial, and wound-healing qualities are provided by these phytoconstituents. ^{[14, 16]}

Calendula officinalis extracts have been demonstrated in experiments to promote fibroblast proliferation, collagen deposition, neo-angiogenesis, granulation, and re-epithelialization, all of which can aid in tissue repair. It is regarded as a suitable herbal ingredient to use in topical treatments like wound dressings, hydrogels, lotion, or herbal foot crack sheets because of its anti-inflammatory, moisturizing, and regeneration qualities. ^{[14, 16]}

7.3.2 Pharmacological Functions

Calendula officinalis exhibits a broad spectrum of pharmacological activities that contribute to its effectiveness in wound healing and skin protection. It accelerates wound healing by promoting fibroblast proliferation, collagen synthesis, granulation tissue formation, and epithelial regeneration, thereby facilitating tissue repair. ^[14,16] The plant also possesses potent anti-inflammatory properties, primarily attributed to its triterpenoids, which inhibit inflammatory pathways such as cyclooxygenase (COX) and lipoxygenase (LOX), leading to reduced production of prostaglandins and leukotrienes. ^[15,16] In addition, Calendula officinalis demonstrates significant antioxidant activity due to the presence of flavonoids and carotenoids, which scavenge reactive oxygen species (ROS), protect skin cells from oxidative damage, and promote tissue regeneration. ^[15,16] The flower extracts also exhibit broad-spectrum antibacterial and antifungal activities against various Gram-positive and Gram-negative bacteria and fungi, thereby helping to prevent secondary infections in damaged skin. ^{[14, 16]} Furthermore, Calendula officinalis promotes angiogenesis by enhancing blood flow to injured tissues, ensuring an adequate supply of oxygen and nutrients required for efficient wound healing. ^{[14, 16]} Its skin-protective action further supports the maintenance of skin hydration and elasticity while reducing transepidermal water loss, making it particularly beneficial in the management of dry skin conditions such as cracked heels.^[15]

7.3.3 Calendula Officinalis's Mechanism of Action

Calendula officinalis's mode of action has not yet been thoroughly investigated. Calendula mayonnaise's active ingredients contain a variety of pharmacological effects related to composition, including anti-inflammatory and anti-alolgenic properties, which are strengthened when the flowers are utilized. These effects include the facilitation of wound healing.

Calendula officinalis's ability to heal wounds is a general word that encompasses a number of biological mechanisms involved in tissue regeneration and repair. By stimulating the phosphoinositide 3-kinase-dependent pathway, flower extracts promote fibroblast migration and proliferation, which increases collagen synthesis and connective tissue formation. ^{[14, 16]}

Furthermore, fibroblast stimulation, granulation tissue formation, and extracellular matrix remodeling caused the wound to contract along with an increase in blood vessel formation. This improved oxygen and nutrient supply to the affected tissue by stimulating angiogenesis, which accelerated tissue repair ^[14,16]

7.3.4 Uses oF calendula officinalis

Calendula officinalis is widely incorporated into pharmaceutical, cosmetic, and dermatological formulations because of its wound-healing and skin-protective properties. It is commonly used for the treatment of cracked heels and foot fissures, wound healing, burn management, surgical wound care, pressure ulcer management, diabetic wound care, skin inflammation, eczema, and dermatitis. In addition, it is an important ingredient in cosmetic creams and lotions, herbal wound dressings, hydrogel formulations, and herbal foot crack sheets. ^[14,16]

7.3.5 Processing of Calendula officinalis

The first step in processing Calendula officinalis is gathering completely opened flower heads, which are then cleaned to get rid of dust, insects, and other foreign objects. In order to protect heat-sensitive flavonoids and essential oils, the blossoms are subsequently shade-dried at temperatures below 40°C. The dried flowers are ground into a coarse powder and extracted with water, ethanol, methanol, or hydroalcoholic solvent (70% ethanol). The extract is then concentrated under low pressure using rotary evaporation after being filtered using muslin cloth and Whatman filter paper. The concentrated extract is then freeze-dried or spray-dried to produce a stable powdered extract, which is subsequently kept at room temperature in airtight, light-resistant, moisture-proof glass containers to preserve its stability and bioactivity. ^[15]

7.3.6 Advantages in Herbal Foot Crack Sheet

Calendula officinalis offers several advantages when incorporated into herbal foot crack sheets. It accelerates wound healing, enhances collagen formation, reduces inflammation, and provides antibacterial and antifungal protection against secondary infections. Additionally, it improves skin hydration and elasticity, minimizes scar formation, and exhibits excellent compatibility with Aloe vera and Centella asiatica in polyherbal formulations, thereby enhancing the overall therapeutic efficacy of herbal foot crack sheets. ^[14,16]

7.4 Curcuma Longa

Figure 7 Curcuma longa

Table 4. Botanical, Physicochemical, Phytochemical, and Pharmacological Profile of Curcuma Longa L. ^[17–20]

7.4.1 Introduction

The perennial herb Curcuma longa L., also known as turmeric (Family: Zingiberaceae), is indigenous to southern and southeast Asia. This herb, which is widely grown in India, is a significant medicinal plant that has been used to treat burns, wounds, skin infections, inflammation, and other conditions in Ayurveda, Siddha, Traditional Chinese Medicine, and Unani. The majority of the herb's significant, bioactive components with a wide range of pharmacological effects are found in the rhizomes. ^{[17, 18]}

Curcuminoids, which include curcumin, demethoxycurcumin, and bisdemethoxycurcumin in addition to several volatile oils including ar-turmerone, -turmerone, and -turmerone, are responsible for the majority of Curcuma longa's therapeutic benefits. They have potent antibacterial, antioxidant, anti-inflammatory, and restorative properties. ^{[17, 18]}

Additionally, curcumin regulates several molecular processes related to wound healing, including angiogenesis, fibroblast proliferation, collagen synthesis, transcription factors, growth factors, inflammatory cytokines, and epithelialization ^[19] Curcuma longa is a useful addition to therapeutic poultices, ointments, hydrogels, nanofibers, wound dressings, and herbal foot crack strips for topical chronic skin ulcers and cracked heels because of these positive effects ^[20]

7.4.2 Pharmacological Functions

Curcuma longa possesses a wide range of pharmacological activities that contribute to its therapeutic potential in wound healing and skin repair. Curcumin, its principal bioactive constituent, accelerates wound healing by promoting granulation tissue formation, collagen synthesis, fibroblast proliferation, wound contraction, and epithelial proliferation, thereby facilitating tissue regeneration. ^{[19, 20]} In addition, curcumin exhibits potent anti-inflammatory activity by inhibiting NF-κB activation and downregulating the expression of inflammatory mediators, including cyclooxygenase-2 (COX-2), lipoxygenase (LOX), tumor necrosis factor (TNF-α), interleukin (IL)-1, IL-6, and inducible nitric oxide synthase (iNOS), thereby reducing excessive inflammation during wound healing. ^{[19, 20]} Curcuma longa also demonstrates strong antioxidant activity, as curcuminoids effectively scavenge reactive oxygen species (ROS) while enhancing the activities of endogenous antioxidant enzymes such as catalase, glutathione peroxidase (GSH-Px), and superoxide dismutase, thereby strengthening the body's natural antioxidant defense system. ^[20] Furthermore, the plant exhibits broad-spectrum antibacterial, antifungal, and antiviral activities against various pathogenic microorganisms, helping to prevent wound infections and promote tissue repair. ^{[17, 19]} Curcumin also promotes angiogenesis by increasing vascular endothelial growth factor (VEGF) expression, which enhances neovascularization and improves the delivery of oxygen and nutrients to regenerating tissues. ^{[19, 20]} Additionally, its antioxidant properties protect skin cells from oxidative damage, support tissue regeneration, improve skin elasticity, and may reduce excessive scar formation during the healing process. ^[20]

7.4.3 Curcuma Longa Mechanism of Action

Curcuminoids, particularly curcumin, which is one of the most powerful natural modulators of various molecular signaling events linked to inflammation, oxidative stress, vascular remodeling, and tissue regeneration, are primarily responsible for Curcuma longa's wound-healing properties ^[19,20]

Curcumin promotes Nrf2-dependent antioxidant pathways while blocking NF-B-mediated pro-inflammatory signaling, which reduces inflammatory cytokines and mediators. ^[20]

Furthermore, it is thought that curcuminoids reduce inflammation by modifying the angiogenic pathways associated with VEGF, which promotes neovascularization and supplies oxygen to ischemic regions. ^{[19, 20]}

Through its anti-inflammatory properties, antioxidant activity, angiogenesis stimulation, increased collagen synthesis, and tissue regeneration, Curcuma longa generally promotes wound healing. ^{[19, 20]}

7.4.4 Uses of Curcuma longa

Curcuma longa is widely used in pharmaceutical and cosmetic formulations because of its wound-healing, anti-inflammatory, and skin-regenerative properties. It is commonly employed in the treatment of cracked heels and foot fissures, acute and chronic wounds, burns, diabetic foot ulcers, pressure ulcers, surgical wounds, and skin infections. In addition, it is incorporated into anti-inflammatory topical preparations, cosmetic creams and gels, hydrogel wound dressings, nanofiber wound dressings, and herbal foot crack sheets. ^[17,19]

7.4.5 Processing of Curcuma Longa

After seven to nine months of growing, the well-developed rhizomes of Curcuma longa are collected and thoroughly cleaned to get rid of soil and other contaminants. After that, the rhizomes are cooked for 30 to 45 minutes to improve curcuminoid stability, gelatinize starch, improve color, and lessen raw odor. The rhizomes are boiled and then dried in the sun or hot air until the moisture content is less than 10%. Before being extracted using hydroalcoholic, ethanolic, methanolic, or supercritical CO2 extraction techniques, the dried rhizomes are sliced and ground into a fine powder. The extract is then filtered to eliminate insoluble components, concentrated by rotary evaporation at low pressure, and freeze-dried or spray-dried to produce a stable powdered extract. Finally, the extract is stored in airtight, light-resistant, moisture-proof containers at low temperature to preserve its stability and bioactivity. ^[18]

7.4.6 Advantages in Herbal Foot Crack Sheet

Curcuma longa offers numerous advantages when incorporated into herbal foot crack sheets. It accelerates wound healing through enhanced collagen synthesis and tissue regeneration, exhibits strong anti-inflammatory and potent antioxidant activities, and provides broad-spectrum antimicrobial effects that help prevent wound infections. Additionally, it promotes angiogenesis, reduces scar formation, and is highly compatible with other medicinal plants such as Aloe vera, Centella asiatica, Calendula officinalis, and Azadirachta indica (Neem) in polyherbal formulations. Its suitability for incorporation into hydrogel and sheet-based wound dressings further supports its application in the management of heel fissures and other chronic skin wounds. ^[19,20]

7.5 Azadirachta Indica

Figure 9 Azadirachta indica

Table 5. Botanical, Physicochemical, Phytochemical, and Pharmacological Profile of Azadirachta Indica A. Juss. ^[21–23]