Potential of Bioactive Compounds for Atopic Dermatitis

Ankita Sahu¹, Manju Singh¹, Vishal Jain¹, Veenu Joshi², Amber Vyas^1*

¹University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh

²Centre of Basic Science, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh

ABSTRACT

Atopic Dermatitis (AD) is a complicated condition that places tremendous physiological and psychological strain on individuals. Natural products have long been used to cure diseases such as cancer, asthma, gastrointestinal disorders, neurological disorders, and infections. The study findings reveal that natural compounds, particularly quercetin, gallic acid, and ginsenosides, have promised preventive effects against atopic dermatitis. The study addresses the medicinal properties of bioactive compounds and emphasizes their ability to exert anti-inflammatory action. These compounds exhibit anti-inflammatory properties by reducing the quantity and functionality of various inflammatory cells such as cytokines neutrophils, monocytes, lymphocytes, Langerhans cells, interleukins (ILs, such as IL-1 IL-5, and IL-4, IL-13, and IL-31), TNF-α, TSLP, and IgE, etc. The studies would pave the way for the development of natural compounds specifically designed to treat atopic dermatitis in humans. Atopic dermatitis is routinely treated using bioactive and phytoconstituents derived from them. As a result, the review emphasizes recent advances in understanding the clinical characteristics, etiology, pathogenesis, treatment with bioactive compounds, and management of atopic dermatitis.

Keywords: Atopic dermatitis, bioactive, anti-inflammatory, natural products, pathogenesis.

 1.     Introduction

Atopic Dermatitis (AD) is widespread and prevalent marked by inflammation that mostly affects young children. It is a chronic skin illness that manifests as recurring episodes of intense itching, irritation, dryness, and thickened skin. It is commonly known as atopic eczema, a persistent inflammatory skin condition associated with xerosis, eczematous lesions occurring in various reason of the body, strong itching, and elevated IgE serum levels (IgE-induced hypersensitivity)(Cláudia Paiva-Santos et al. 2022) (Egawa and Weninger 2015). According to the National Survey of Children's Health, it is a prevalent health concern that affects 8.7% to 18% of the population. Because of its chronic and painful symptoms, Atopic dermatitis is a significant healthcare concern. The term "atopy" describes a hereditary propensity to develop immunoglobulin E (IgE) antibodies in response to minute amounts of typical environmental proteins, such as pollen, house dust mites, and food allergies. The Greek terms "derma" and "itis," which both indicate "inflammation," are the origin of the word "dermatitis." For example, the French dermatologist Ernest Besnier (1831-1909) coined the term "prurigo Besnier" to describe the condition, which translates as "Besnier's itch"(Thomsen, Simon Francis 2014). The main problems related to atopic dermatitis are given in Figure 1:

  Figure 1: Problems of atopic dermatitis

Atopic dermatitis is distinguished by a dysfunctional skin barrier and aberrant immunological responses, notably the Th2/Th22-deviated response. Allergens can enter the skin through the skin barrier disruption and dehydration produced by genetic abnormalities in the filaggrin (FLG) gene. These disruptions, coupled with dehydration, trigger the production of thymic stromal lymphopoietin (TSLP) by the epidermis, which further activates the Th2/Th22. This shift in immune response is accelerated as the disease progresses from acute to chronic phase. During the chronic phase of atopic dermatitis, Th1 cells, rather than Th17 cells, play a role in the immune response. Th2 cells produce cytokines such as interleukin 4 (IL-4) and interleukin 13 (IL-13) which stimulate antibody-producing cells (B cells) to generate Immunoglobin-E(Ig-E) antibodies against allergens. Some IgEs also exhibit autoreactivity, further exacerbating the disease activity by reacting to self-antigens. The compromised epidermal barrier is harshed by the potent suppressors of FLG expression found in IL-4, IL-13, and IL-22. Itching is a result of TSLP and Th2-derived IL-31, and scratching exacerbates skin barrier breakdown. (Vanessa et al. 2022)(G. Yang et al. 2020)

Atopic dermatitis (AD) is a chronic and commonly fatal disorder that arises from a complex interplay of genetic predisposition, impaired skin barrier function, and immune dysregulation. The influx of calcium, which is controlled by the ORAI1 channel, is required for keratinocytes to secrete TSLP. Targeting the TSLP/Th2/Th22 and ORAI1 pathways could be one method to combating atopic inflammation. Researchers may be able to establish a viable therapeutic strategy for managing this illness as a result of their efforts. The given figure 2 depicts the pathogenesis of atopic dermatitis: (Furue et al. 2017)

 Figure 2: Pathogenesis of Atopic Dermatitis

 1. Available Treatment Strategies for Atopic Dermatitis

Atopic dermatitis treatment is based on the patient's age or the severity of the condition. Corticosteroid creams and ointments are commonly used to treat skin issues and reduce inflammation. Moisturizing creams can help to repair the skin's barrier. Because discontinuing the standard dose of oral corticosteroids can result in an atopic dermatitis flare-up or worsening of the condition. Topical calcineurin inhibitors help to decrease inflammation and avoid flare-ups. A topical cream containing phosphodiesterase-4 inhibitors can help with inflammation when other treatments are ineffective. Much research has been conducted to develop nanocarriers for the topical delivery of drugs for the treatment of atopic dermatitis. These nanocarriers include polymeric nanocarriers, Lipid nanocarriers, micelles, nanoemulsions, transfersomes, etc.(Patel, Patel, and Thakkar 2021). Figure3 shows the treatment goal for atopic dermatitis. Current status of selected agents for atopic dermatitis depicted in Table1:(Weidinger et al. 2018)(Mandlik and Mandlik 2021)

 Figure 3: Treatment Goal of Atopic Dermatitis

 Table 1: Current status of selected agents for Atopic Dermatitis

1.      Role of bioactive in the atopic dermatitis

 Phytoconstituents are naturally occurring organic compounds that are present in plants and have a variety of uses, such as guarding the plant against diseases, predators, illnesses, and other dangers. They also influence the color, flavor, and scent of the plant. These substances can be divided into two categories: active drug ingredients and inert non-drug constituents, and they are produced by both primary and secondary metabolic processes.

The primary phytoconstituent found in plants include alkaloids, terpenoids, phenols, phenolic glycosides, coumarins, coumarin glycosides, anthraquinones, saponins, cardioactive glycosides, cyanogenic, anthraquinone glycosides, flavones, flavonoid glycosides, mucilage and gums, tannins, volatile oils, etc. These phytoconstituents play a crucial role in the medicinal properties of plants. Among them, flavonoids have been extensively studied and found to possess antioxidant and anti-inflammatory effects. In addition to these active constituents, plants also contain other essential nutrients such as carbohydrates, vitamins, minerals, amino acids, and fibers. Additionally, they may contain sugars, lipids, organic acids, and even antibiotics. These nutrients are necessary for maintaining a healthy body and immune system. Therefore, consuming plants with these beneficial compounds can promote overall health and well-being (Rainsford and Alamgir 2018). There are some bioactive that are used in atopic dermatitis are given below:

3.1 Capsaicin (capsicum annuum)

 Despite having numerous biological benefits, such as anticancer, antioxidant, and antiangiogenic activities. The strong pungency of capsaicin can cause skin irritation and limits its practical usage. However, an alternative non-pungent analog of capsaicin known as capsiate has emerged, possessing comparable biological effects to capsaicin without causing skin irritation. Capsiate's effects on immunological cells and allergic reactions, still have not been thoroughly explored. In a study conducted by JH Lee et al., the researchers explored the impact of capsiate on mouse CD4+ T cells and mast cell activation. The study demonstrated that Capsiate effectively suppressed DNFB-induced atopic dermatitis in mice. Topical capsiate treatment decreased blood IgE levels, and cutaneous chemokine and cytokine activities in DNFB treated mice. Furthermore, it reduced the activation of mast cells and CD4+ T cells, both of which are connected to allergic disorders. Capsicum inhibited the development of T helper type 1 (Th1), T helper type 2 (Th2), and Th17 cells in naive CD4+ T cells. Capsiate therapy decreased the release of pro-inflammatory cytokines and the breakdown of activated bone marrow-derived mast cells by interfering with extracellular signal-regulated kinase signal pathways.(J. H. Lee et al. 2015)

        Figure 4: Capsicum annuum

 3.2 Cordycepin (Cordyceps sinensis)

 Cordyceps are fungi that grow on insects and are highly regarded in Korea, China, and Japan for their therapeutic characteristics. The fungus is thought to have tonic benefits on lifespan, endurance, and vigor, and has been used to treat numerous types of issues such as skin infections, chronic bronchitis, asthma, and tuberculosis. In addition to its anti-oxidant and antiviral capabilities, cordyceps also exhibits anti-cancer, anti-fibrotic, anti-inflammatory, anti-nociceptive, anti-angiogenic, and anti-diabetic effects (G. Wu et al. 2011). A nucleoside antibiotic called cordycepin, which originates from the Cordyceps militaris, is the major bioactive substance. According to Na-Ra Han's research, cordycepin might decrease the severity and clinical symptoms of lesions that resemble AD. In the serum of AD mice, cordycepin significantly reduced the levels of TSLP, IL-6, IL-4, and TNF. Additionally, in skin lesions that resembled AD, cordycepin suppressed CCR-3, MIP-2, ICAM-1, and TARC levels as well as mast cell and eosinophil infiltration. Yoou's study found that cordycepin can decrease caspase-1 expression and activity in AD-related skin lesions while simultaneously lowering TSLP expression (N. R. Han et al. 2018).

                                                        Figure 5: Cordyceps sinensis

 3.3 Crocin (gardenia jasminoides)

 The naturally occurring carotenoid component crocin, which has been discovered to have anti-inflammatory properties, is present in Gardenia jasminoides. According to research, crocin considerably reduced the severity of atopic dermatitis symptoms in NC/Nga mice induced by a crude extract of Dermatophagoides farinae. Ear thickness, serum immunoglobulin E levels, and dermatitis severity all decreased.  Additionally, eosinophil and mast cell infiltration as well as epidermal thickness growth were observed to be affected by crocin in a dose-dependent manner.

Additionally, it has been demonstrated that crocin inhibits the NF-B/STAT6 signaling pathways, which are known to have a role in the etiology of atopic dermatitis, hence reducing the activation of the immune system by Th2 cells. In studies, it was discovered that crocin significantly reduced the symptoms of atopic dermatitis brought on by Dermatophagoides farinae crude extract in NC/Nga mice. Ear thickness, serum immunoglobulin E levels, and dermatitis severity all declined. Additionally, it was discovered that crocin, in a dose-dependent manner, inhibited eosinophil and mast cell infiltration as well as the rise in epidermal thickness. Additionally, it has been found that crocin inhibits the NF-B/STAT6 signaling pathways, which are known to contribute to the etiology of atopic dermatitis, reducing the activation of the immune system's Th2 cell-mediated response (Sung and Kim 2018).

 Figure 6: Gardenia jasminoides

3.4 Chrysophanol (Rumex crispus cordyceps militaris)

 Chrysophanol, a popular herbal medication and functional food in Korea, is manufactured mostly from processed Rumex crispus and Cordyceps militaris. The former is well-known for its ability to treat a variety of ailments, including inflammation, edema, disinfestation, and diarrhea, jaundice, stroke. Chrysophanol, a bioactive molecule discovered from Rumex crispus, exhibits anti-inflammatory effects as well. According to Jeong et al., AST2017-01 and Chrysophanol act as an effective anti-inflammatory in atopic dermatitis in vitro models (N. Han et al. 2018) On the other hand, Cordyceps militaris has been found to have anti-cancer properties  (Jeong, Kim, and Kim 2018).

 3.5 Decursin (angelica sinensis)

Angelica sinensis (AS) (Oliv.) Diels, a plant from the Apiaceae family, has been used for centuries in traditional oriental medicine to manage a variety of skin and circulatory disorders. The medicinal properties of AS root are well-known, including anticancer, neuroprotective, radioprotective, immunoregulatory, and antioxidant effects. Decursin, one of the active ingredients in AS, has been shown to prevent the generation of inflammatory chemicals in macrophages stimulated by lipopolysaccharides. As a result, AS root may be a good choice for the treatment of atopic dermatitis and other inflammatory skin disease (J. Lee et al. 2016).

 Figure 8: Angelica Sinensis

 3.6 Linolenic acid (Coriandrum sativum)

 Coriander, or Coriandrum sativum L. (CS), is a common annual herb from the carrot family that is widely cultivated in Asia and Europe. CS is a popular spice and food seasoning. According to research, CS leaves have anti-inflammatory properties through decreasing nitric oxide (NO) generation produced by lipopolysaccharides in RAW 264.7 macrophages. Additionally, CS exhibits antioxidant properties that guard against UV erythema and oxidative stress-driven on by a high-fat diet in rats. They examined that the linoleic and linolenic acids in Coriandrum sativum can protect human skin keratinocytes from H2O2 oxidative damage. Nuclear factor erythroid-derived 2-related factor regulation of antioxidant defense enzymes including heme oxygenase-1 (HO-1) and total glutathione (GSH) may be responsible for such beneficial effects. Overall, because of its anti-inflammatory and antioxidant qualities, CS is a valuable plant with potential health advantages (Park et al. 2014).

L. Tang et al. demonstrated that various linoleic and linolenic acids ratios, particularly a ratio of 4:1 treatment, effectively reduced DNFB-treated skin lesions, ear edema, scratching behavior, and skin inflammation as evidenced by the reduced inflammatory blood cells, Immunoglobin-E, serum levels, and skin levels of the pro-inflammatory lipid mediators, including LTB4 and PGE2. The scientific basis for the therapeutic value of linoleic and linolenic acids in the clinical management and prevention of AD can be established by their positive effects on symptoms similar to AD (Tang et al. 2020).

 Figure 9: Coriandrum sativum

 3.7 Gallic acid (Cortex moutan)

 Many fruits, including grapes, mangoes, and green tea, contain gallic acid (GA), a polyphenol. These substances, also known as 3,4,5-trihydroxy benzoic acid and hypertension, vascular calcification, cardiac remodeling, and fibrosis, have all been shown to benefit from the use of this chemical. This is thought to be due to the chemical's antioxidant properties, which help to reduce inflammation and free radicals. Anti-inflammatory qualities have been shown by GA in addition to antioxidant benefits. In rheumatoid arthritis, fibroblast-like synovial cells (FLS), GA treatment has been shown to lower levels of proinflammatory cytokines like IL-1 & IL-6, chemokines like CCL-2 & CCL-7, as well as cyclooxygenase-2 (COX-2) & matrix metalloproteinase-9 (MMP-9). The findings suggest that GA might be a useful therapeutic approach for inflammatory disorders. In animal models of allergic rhinitis, GA has additionally been demonstrated to regulate the immunological response, reducing symptoms. Hu and Zhou et al. reported that GA could alleviate skin inflammation through immunomodulation of Th17 in the DNCB-induced AD-like mouse model. Therefore, GA might have the potential to treat AD in the clinic (Hu and Zhou 2021).

 Figure 10: Cortex moutan

 3.8 Geniposide (Gardenia jasminoides)

 Gardenia jasminoides is a well-known medicinal plant with antiphlogistic, analgesic, anti-inflammatory, and antipyretic effects. This plant's fruit is frequently used in traditional medicine formulations to treat a variety of diseases, including inflammation, headache, edema, fever, hepatic problems, and hypertension. It's also used to treat inflammatory conditions like gastritis, dermatitis, and aphthous stomatitis. Additionally, Gardenia jasminoides have been found to inhibit vascular inflammation induced by tumor shanzhiside, scandoside methyl ester, deacetyl-asperulosidic acid methyl ester, and genipin-1-β-D-gentiobioside. Recent research has shown that geniposide has anti-asthmatic properties in a mouse model of ovalbumin-induced allergic airway inflammation. Despite several studies on Gardenia jasminoides' physiological effects, its ingredients and potential benefits in lowering allergic skin inflammation and alleviating symptoms of atopic dermatitis (AD) have yet to be properly examined (Sung, Lee, and Kim 2014).

3.9 Gintonin (Panax ginseng)

 Numerous immunomodulatory properties of ginseng, a conventional herbal remedy, have been discovered to be advantageous to human health. Animal models used in the studies have demonstrated that ginseng has anti-allergic, anti-scratching, and anti-atopic dermatitis properties. It has been discovered that ginseng extract, or ginseng saponin fraction, which may be prepared using a variety of extraction techniques, has therapeutic effects in the treatment of skin conditions, including anti-atopic dermatitis properties. Gintonin, a substance produced from ginseng, functions as both an ATX inhibitor and an LPA receptor ligand. Recent studies suggest that plasma ATX may contribute to skin disorders. For instance, the expression of ATX is elevated in allergic asthma and is likely to play a substantial part in the development of atopic dermatitis in humans. Compared to healthy controls, patients with cholestatic pruritus and atopic dermatitis have greater serum ATX activity. The results suggest that ATX may become a future target for drugs intended to treat human atopic dermatitis (B. H. Lee et al. 2017).

 Figure 11: Panax ginseng

 3.10 Indirubin (polygonum tinctorium)

 Traditional Korean medicine has utilized Naju Jjok, also known as Polygonum tinctorium Lour., for the management of a number of skin conditions. Furthermore, Niram, a natural textile dye derived from Naju Jjok, has been used for many years in Korea. Despite its historical use, the preventative effects of Niram against atopic dermatitis are unclear. S. Wu et al. investigated and tested indirubin's therapeutic efficacy in DNCB-induced AD-like mice. Serum IgE levels and cytokine production, including TNF-, IL-4, IL-6, and IFN-, were drastically reduced in DNCB-affected AD-like lesions following indirubin treatment. It also controlled the activation of NF-B and IKB and the normalization of MAP kinase signal transduction. Based on the findings, Indirubin may become a useful drug for treating allergic dermatitis by suppressing the development of Th1 and Th2 cell immunological responses  (S. Wu et al. 2021).

 Figure 12: Polygonum tictorium

 3.11 Naringenin (tomatoes, cherries, grapefruit)

 Naringenin is a flavonoid found in citrus fruit peels, grapes, and tomatoes that has several health benefits. It contains antioxidative, anti-atherogenic, and anti-cancer characteristics as well as anti-inflammatory capabilities by decreasing the synthesis of nitric oxide and prostaglandin E2. According to recent research, naringenin can limit picryl chloride-induced contact hypersensitivity by reducing T cell proliferation and activation. It has also been shown to inhibit the production of thymic stromal lymphopoietin in mast cells. Additionally, it has been demonstrated to prevent mast cells from producing thymic stromal lymphopoietin. However, no studies on the impact of naringenin on AD-like skin lesions in NC/Nga mice have been done. Molecular weight of naringenin is 272.3 g/mol and has log P value 2.6, demonstrating its lipophilic nature. Thus, it has low solubility in water and is difficult to absorb orally. Due to its anti-inflammatory, antioxidant, antiallergic, photoprotective actions, naringenin is pertinent flavonoid for atopic dermatitis treat (Nagula and Wairkar 2020).

Figure13: tomatoes, cherries, grapefruit

 3.12 Oregonin (Alnus japonica)

Since ancient times, Americans have utilized the Alnus species plant, a member of the Betulaceae family, as a folk treatment for a variety of skin issues, including prurigo, eczema, and persistent herpes. A number of diarylheptanoids, including 1,7-bis-(3,4-dihydroxy phenyl)-heptane-5-O-d-glucopyranoside, 1,7-bis-(3,4-dihydroxy phenyl)-5-hydroxy heptane, and others, were recently isolated from the plant. Among these compounds, oregonin has been demonstrated to have significant antioxidant activity by scavenging free radicals, reducing the production of nitric oxide and prostaglandin E2, and suppressing the expression of cyclooxygenase-2. Additionally, oregonin has been shown to suppress the production of reactive nitrogen species, IL-12, p70, and TNF-alpha, among other proinflammatory molecules. Oregonin has also been demonstrated in vitro to reduce calcium rise. In addition to these advantages, oregonin has been revealed to be effective in reducing the signs and symptoms of atopic dermatitis. Overall, the Alnus species plant and its components, especially oregonin, have enormous potential as natural treatments for a range of inflammatory illnesses and skin conditions (Choi et al. 2011).

  Figure 14: Alnus japonica

 The white wax scale beetle (Ericerus pela, Chavannes), which has been bred in China for over a century, is well-recognized for its capacity to yield wax. The capillary zone electrophoresis technique revealed that this crude polysaccharide, known as CWPS, comprises glucose, mannose, and galactose. Recent investigations have shown that CWPS, which is derived from female white wax scales, has typical anti-inflammatory, antioxidant, and anti-cancer functions. To investigate the potential use of CWPS for treating skin inflammatory diseases, researchers orally administered CWPS to a BALB/c mouse model induced with 2,4-dinitrochlorobenzene (DNCB) to mimic AD-like symptoms. They intended to discover if CWPS could help with AD-related symptoms such as if CWPS could help with AD-related symptoms such ear swelling, skin lesions, serum IgE levels, and mast cell infiltration. Additionally, they investigated variations in the frequency of Th1, Th2, and Th17 cells in the spleen as well as variations in the expression of IFN-c, IL-4, and IL-17 mRNA in the dorsal skin and ear (Lin et al. 2017).

  Figure 15: Ericerus pela

 3.14 Quercetin (Dendrobium taense)

 Dendrobium, an Orchidaceae member with about 1600 species, has been used in traditional Chinese and folk medicine for its antipyretic, ophthalmic, and tonic properties. The well-known "Shi-hu" (Dendrobium spp. or Herba Dendrobii) is produced from the stems of many Dendrobium species and is well-known for its many medical benefits. The presence of a number of compounds, including flavonoids, phenanthrenes, bibenzyls, fluorenones, sesquiterpene alkaloids, and polysaccharides, is credited with these benefits. In a recent study, its anti-inflammatory, antioxidant, anti-cancer, anti-aging, anti-diabetic, and antiallergenic properties were highlighted (C. T. Wu et al. 2014). Quercetin is a naturally occurring polyphenol flavonoid with a high antioxidant content. It has well-known anti-allergic qualities that stop the release of histamine and pro-inflammatory mediators. Quercetin can reduce the amount of IgE antibodies made by B cells in response to an antigen and regulate the stability of Th1/Th2 responses. Quercetin plays a key role in immunomodulatory and anti-inflammatory functions, allowing it to be used to treat a range of diseases. The cytokines IL-4, IL-5, and IL-13 were downregulated, as were cytoplasmic, RAGE, HMGB1, nuclear p-NF-B, COX2, TNF, IL-1, IL-2R, IFN, p-extracellular signal-regulated kinase (ERK) 1/2 and IL-4. Nuclear Nrf2 was upregulated, and quercitin suppressed Th2-related cytokine expression and angiogenesis (Jafarinia et al. 2020).

 Figure 16: Dendrobium tosaense

3.15 Resveratrol

Resveratrol is a polyphenol that occurs naturally in different types of fruits and vegetables, with red grape skin being a notable source. It has been the subject of several studies which have demonstrated its potential pharmacological effects, including anti-inflammatory, antioxidant, antiangiogenic, and anticancer properties. Recent studies investigated the impact of resveratrol treatment on keratinocyte apoptosis and cytokines derived from keratinocytes using a murine model of 2,4-dinitrophenyl benzene (DNFB)-induced lesions that resemble atopic dermatitis (Y. S. Lee et al. 2020).

  Figure 17: Resveratrol

 3.16 Valencene (Cyperus rotundus)

 Cyperus rotundus L. is a medicinal herb that has been traditionally used to treat various health issues, including gastric ailments, cognitive disorders, inflammation, and wounds. One of the major bioactive compounds present in this plant is Valencene, which is a sesquiterpene known for its therapeutic properties. Studies have shown that VAL possesses antioxidant, antiseptic, and antiallergic activities, making it a promising candidate for the treatment of inflammatory skin conditions like atopic dermatitis. In vitro studies on HaCaT cells and RAW 264.7 cells have confirmed the anti-inflammatory effects of valencene. Specifically, it has been found to reduce the expression of proinflammatory cytokines and chemokines. Furthermore, the underlying mechanisms of these effects have been investigated, and it has been found that valencene has a positive impact on skin barrier functions. It promotes the expression of key skin barrier proteins such as filaggrin, loricrin, and involucrin, which are essential for maintaining healthy skin. Overall, valencene holds great potential as a therapeutic agent for the treatment of inflammatory skin disorders like AD. Its anti-inflammatory and skin barrier-enhancing properties make it a promising candidate for further research and development in this field (I. J. Yang, Lee, and Shin 2016).

 Figure 18: Cyperus rotundus

 3.17       Curcumin (Curcuma longa)

 The active component of turmeric, curcumin, is a polyphenolic molecule that is derived from the roots of the Curcuma longa plant. It is a member of the family Zingiberaceae (Kumar et al. 2023). Our results imply that systemic administration of curcumin can have anti-inflammatory and antioxidant benefits in AD mouse models. Additionally, there is data that curcumin may be a viable therapeutic drug for slowing the march of atopic dermatitis due to the inhibition of AD-related allergic airway inflammation following exposure to aerosolized OVA (Sharma, Sethi, and Naura 2020).

Figure 19: Curcuma Longa

 3.18         Beta-pinene (alpinia intermedia)

 Alpinia intermedia, a member of the Zingiberaceae family of plants, has long been used by people in southern Japan to make Japanese Kampo medicine, shield clothing from pests, and preserve food. Recent research has suggested that specific Alpinia strains may have anti-inflammatory qualities that can aid NC/Nga mice with dermatitis brought on by house dust mites. These results led to the hypothesis that A. intermedia extracts might be helpful for atopic dermatitis. Y. Amagai et al. looked at the clinical outcomes of NC/Tnd mice given Zingiberaceae plant extract treatment. As a result of reducing neurite outgrowth as well as mast cell and keratinocyte activation, the results demonstrated that A. intermedia extracts and their main constituent, b-pinene prevented the development of AD. B-pinene's inhibitory properties were also proven in vitro and in vivo. According to the results, applying an A. intermedia extract topically to the skin of NC/Tnd mice enhanced skin health by reducing the number of inflammatory reactions. The extracts might develop into distinctive atopic dermatitis skin care products. The results showed that A. intermedia extracts and their main constituent, b-pinene, helped to prevent the onset of AD by decreasing neurite outgrowth and keratinocyte and mast cell activation (Amagai et al. 2017).

 Figure 20: Alpinia intermedia

 3.19       Astaxanthin

 Microalgae and crustaceans like krill and prawns typically contain the xanthophyll carotenoid known as astaxanthin (AST). Through its significant anti-inflammatory and antioxidant effects, numerous studies have shown its pharmacological usefulness in treating a variety of ailments, including cardiovascular, gastrointestinal, hepatic, neurological, and skin disorders. Some studies have shown that in the case of ethanol-induced liver injury and lipopolysaccharide-induced neuroinflammation, AST can effectively decrease oxidative stress and inflammation via inactivating STAT3 and NF-kB. The benefits of using AST topically include fewer adverse effects and drug misuse, eliminating first-pass metabolism, and allowing for high-dose administration. Topical application is also well suited for sustained and regulated distribution over an extended period, making it a great choice for skin conditions when it's necessary to apply the medication directly to the area of irritation. However, AST's limited water solubility restricts its ability to be applied topically. A liposomal formulation that can improve the solubility of AST by conjugating it with phospholipid structures has been created to solve this problem, enabling effective topical administration (Y. S. Lee et al. 2020).

3.20     Baicalein

 A flavonoid-structured active ingredient of Scutellariae radix is called baicalein. Baicalein is a flavonoid-structured active component of Scutellariae radix. There are now many different pharmacological activities that have been described, including antioxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Mi-Young Yun conducted research in order to better understand how a hydrolyzed version of baicalin, affects dermatitis that resembles AD and inflammatory cytokines connected to the hypersensitive immune response in NC/Nga mice AD tissues. Both the rate of immune cell infiltration and the thickness of the epidermis/dermis were significantly decreased after 8 weeks of topical therapy with baicalein hydrogels. Further research led them to the conclusion that baicalein can treat atopic dermatitis by regulating the balance of Th1 and Th2 cells by reducing the production of IL-4, IL-6, and TNF- and increasing the expression of IFN-. Baicalein has been shown by Kuo-Feng Huang et al. to stimulate ERK phosphorylation, Ca2+ influx, and the expression of K1 and K10 via activating TRPV4. The actions of baicalein on keratinocyte differentiation and proliferation regulation assist in repairing the skin barrier and reversing AD-like skin lesions (Yun et al. 2010).

Figure 22: Scutellariae radix

 2.      Future Prospects

 Natural products have long been a rich source of chemicals for therapeutic development, and their efficacy and safety in the treatment of atopic dermatitis have been extensively researched. Based on the research, various natural products have demonstrated potential in the treatment of atopic dermatitis, both systemically and topically. Some natural compounds, such as baicalein, quercetin, piperine, indirubin, gallic acid, and ginsenoside, have undergone clinical trials, whereas others, such as naringenin, resveratrol, and ginsenosides, have been developed into pharmaceutical preparations and are frequently used to treat a variety of illnesses. Overall, the majority of these natural compounds have been shown to be safe for use in the treatment of atopic dermatitis. Because natural compounds have multi-target and multi-pathway effects, combining their use may provide more effective pharmacological options for treating atopic dermatitis.

 3.      Conclusions

 The following is a summary of a survey of herbal remedies with therapeutic potential for treating dermatitis and relieving patient discomfort. These plants include active components that are responsible for a variety of pharmacological activities, including modulation of skin barrier homeostasis, permeability, and inflammation. Some plant extracts are also humectants or moisturizers for dry skin. While no clinical experiment has thoroughly confirmed the efficiency of herbal formulations, there is hope that these plants will eventually become powerful therapeutic aids in the treatment of chronic and painful skin disorders. Overall, the analysis reveals that medicinal plants have the potential to provide treatment and improve the quality of life for eczema patients.

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