ABSTRACT:

Chemotherapeutic patients often experience skin-related side effects such as dryness, itching, and inflammation due
to the treatment. In this study, we formulated an Ayurvedic skin ointment containing punarnava, deodar, aloevera,
turmeric, and rosemary, known for their anti-inflammatory and healing properties. The aim of this study was to
evaluate the efficacy of the ointment in providing relief to patients suffering from skin issues caused by
chemotherapy. The ointment was formulated using a combination of these herbal ingredients in a suitable base.
Physicochemical parameters such as pH, viscosity, and spreadability were determined to ensure the stability and
usability of the ointment. The ointment was then evaluated for its anti-inflammatory and healing properties using in
vitro and in vivo studies. The results of the study showed that the Ayurvedic skin ointment containing punarnava,
deodar, aloevera, turmeric, and rosemary was effective in reducing inflammation and promoting healing in
chemotherapeutic patients. The ointment was well-tolerated, with no adverse reactions reported by the patients.
Overall, this study demonstrates the potential of Ayurvedic herbal formulations in providing relief to
chemotherapeutic patients experiencing skin issues. Further research is needed to explore the long-term benefits and
safety of this ointment for use in clinical settings.

Key Points:
AIM: Formulation and Evaluation of Ayurvedic Skin Ointment for Chemotherapeutic Patients.

OBJECTIVE:

 The objective of formulating and evaluating an ayurvedic skin ointment for chemotherapeutic
patients is to provide a natural and effective treatment option for managing skin-related side
effects of chemotherapy.
 Chemotherapy often leads to various skin issues such as dryness, itching, rashes, and
inflammation, which can significantly impact the quality of life of patients undergoing
treatment.
 By formulating an ayurvedic skin ointment using natural ingredients known for their soothing
and healing properties, such as neem, turmeric, aloe vera, and licorice, the aim is to provide
relief from these skin issues and promote healing without causing further harm or irritation to
the sensitive skin of chemotherapy patients.
 The evaluation of the efficacy and safety of the ayurvedic skin ointment will involve
conducting clinical trials and user studies to assess its impact on various skin conditions
commonly experienced by chemotherapy patients.
 This will help determine the effectiveness of the ointment in providing relief from symptoms,
improving skin health, and managing side effects of chemotherapy treatment.
 Overall, the objective is to develop a natural and holistic approach to skincare for
chemotherapeutic patients that complements their cancer treatment and supports their overall
well-being during a challenging time.
INTRODUCTION:

ANATOMY AND FUNCTION OF SKIN:

Skin is outer covering of the body & is the largest organ of the body. It is covering an impressive surface area of
approximately 2 m2, accounting for about 20% of total adult body weight [1]. It performs many vital functions like
protection against external physical, chemical and biologic assaulter. It play important role in prevention of excess
water loss from the body and a role in thermoregulation [2]. It cover and protecting our entire body. The skin plays a
crucial role in immunologic surveillance, sensory perception, control of insensible fluid loss & Homeostasis [3] [4].

[ GROSS STRUCTURE OF SKIN]

The skin is composed of three layers: the epidermis, the dermis, and subcutaneous tissue [2].

 The Epidermis: The outer layer of skin, provides a waterproof barrier & contributes to skin tone. It composed
of several layers of cells, including keratinocytes, which produce the protein keratin that provides strength
and waterproofing to the skin. The epidermis also contains melanocytes, which produce the pigment melanin
that gives the skin its color and helps protect against UV radiation. The Epidermis is Divided into five layers:
Stratum Basale, Stratum Granulosum, Stratum Lucidum & Stratum Corneum.
▪ Stratum corneum: This layer consists of fully fullgrown keratinocytes which contain tough proteins. The
outermost layer could even be a continuously shed. The corneum which prevents the entry of most foreign
substances also because of the loss of fluid from the body.
 ▪ Keratinocytes (squamous cells) this layer, beneath the stratum corneum, contains living keratinocytes
(squamous cells), which mature and form the stratum corneum.
▪ The basal layer is the deepest layer of the epidermis, containing basal cells. The basal cells continually
divide, forming new keratinocytes and replacing the old ones that are shed from the skin's surface [3] [4].
The epidermis consist of a specific constellation of a cells called as Keratinocytes. Which function to
synthesize a keratin that is a long thread like protein with protective role [2].
• The Dermis: It found beneath the epidermis which composed of connective tissue, hair follicles, blood
vessels, lymphatic vessels & sweat glands. It gives the skin its strength and elasticity. The Dermis is divided
into two layers, the Papillary dermis (the upper layer) & the reticular dermis (the lower layer) .The dermis is
the center layer of the skin. The dermis contains the following:
➢ Blood vessels
➢ Lymph vessels
➢ Hair follicles
➢ Sweat glands
➢ Collagen bundles
➢ Fibroblasts
Nerves Collagen protein made by fibroblasts held together with a dermis layer. This layer gives flexibility
and strength to the skin. It also contains pain and touch receptors [3] [4].
• Hypodermis / Subcutaneous tissue: It consists of fat and connective tissue that provide insulation and
cushioning for the body. It is a layer of loose connective tissue & elastin which provide insulation from cold
temperature, shock adsorbent capability, nutrient & energy storage reservoir. The subcutis Is the genuine
layer of skin [5].

Function of skin: [2] [3] [5]

The skin is the body’s largest organ, and that they cover the whole body. They even have protected the body against
infection, heat, injury, and lightweight the skin also;

• Regulation and control of blood heat

• Water and fat are stored

• Perform as a sensory organ

• Reduce the water loss

• Protect from chemical, microbiological and chemical attack

• Protect against the entry of bacteria

• Stop access to noxious foreign substance and radiation All over the body, the skin has many characteristics. the top
having more hair follicles, while the soles of the feet contain none. In calculation, the soles of the feet and palm of
hands are thicker . • The skin acts as a barrier to protect the body from harmful pathogens, UV radiation, and
environmental toxins.

• It also helps to prevent excessive water loss and regulates body temperature.

• The skin contains sensory receptors that allow us to feel touch, pressure, temperature, and pain. The skin plays a
crucial role in regulating body temperature. Sweat glands in the skin produce sweat, which helps cool the body when
it's hot, while blood vessels in the skin constrict or dilate to help regulate body temperature in response to changes in
the environment.

• When exposed to sunlight, the skin is capable of producing vitamin D, which is essential for bone health and
overall immune function.

• As a barrier against infectious agents and initiating immune responses when necessary to protect against infections.

• The skin helps to eliminate waste products from the body through sweat, which contains some metabolic waste
products and toxins.

BACKGROUND:

Burns are skin injuries that require close observation during the entire healing process. They are typically brought on
by extreme heat, electricity, radioactivity, or corrosive chemicals. They have become a major global public health
concern, resulting in an estimated 180,000 deaths every year. Burns can cause physical impairments as well as mental
and emotional issues, all of which are very costly to communities [6]. The creation of granulation tissue,
inflammation, re-epithelialization, and extracellular matrix remodeling are the several stages of the intricate process
of burn wound healing. Despite the development of a wide range of antiseptics, infections have been identified as one
of the primary factors impeding the healing of wounds, and they continue to be a challenge to contemporary medicine
[7]. Through various methods of action, natural compounds have demonstrated promising qualities in the process of
wound healing [8]. Extracts [9–12], essential oils [13, 14], and secondary metabolites [15] isolated from medicinal
plants were found to be effective. Even with advanced skin-sparing procedures, radiation-induced skin responses are
still a typical side effect of radiotherapy treatment for cancer. Simultaneous radiation and chemotherapy can raise the
chance of an unfavorable reaction even more [16]. Between 87% and 96% of women receiving radiation therapy for
breast cancer are thought to have had skin responses [17] [18]. Responses range from moist desquamation to
moderate erythema [17]. Radiation fractionation, total dosage, anatomic treatment region, radiation energy, and
individual patient variables like smoking and obesity all affect how severe a skin reaction will be [19] [20] [21]. Not
only are skin burns a frequent side effect of therapeutic radiation, but they also rank as the most frequent injury in
incidents involving radiation exposure [22, 23]. The skin, which covers the entire body, suffers quick and serious
damage from radiation exposure in radiotherapy, even if many other tissues and organs are also impacted [ 24].
Furthermore, interest in finding novel strategies to lessen radiation-induced tissue damage has increased due to the
side effects of irradiation in an increasing number of cancer survivors as well as the necessity for medical
countermeasures against radiologic or nuclear mishaps and terrorism [25]. Many interesting substances have been
studied for their ability to prevent radiation-related damage [26, 27, 28, 29].
{Schematic diagram showing different intrinsic and extrinsic biological/molecular events
potentiating the transformation of a normal cell to the cancer cell, while the lower part of this
diagram showing different hallmarks of a transformed cancer cell. [30]}
LITERATURE REVIEW:

INVESTIGATORS TITLE OF ARTICLE MAJOR CONCLUSION

Bihari Dora B et al, Punarnava (Boerhavia diffusa): A Promising Punarnava is one of the potent
Indigenous Herbal Drug and Its Effect on herbal drugs which give us the
2015 [42]
Different Disease Conditions knowledge about its various
properties and formulations being
used as Anti-inflammatory, Anti-
proliferative, Antibacterial, Anti-
stress etc.

Shikha Mishra et al, Phytochemical, Therapeutic, and BD contain diverse chemical

2014 [55] Ethnopharmacological Overview for a compounds which has shown
Traditionally Important Herb: Boerhavia diffusa therapeutic activities such as,
Linn. Anticancer, Anti-inflammation,
Hepatoprotection and
Immunomodulation.
Mahesh AR et al, Detail Study on Boerhaavia Diffusa Plant for Boerhaavia Diffusa which is having
2012 [56] its Medicinal Importance- A Review a wide range of medicinal value due
to their variety of chemical
constituents can be further
investigated on toxicological and
other parameters to obtain a valuable
marketed product. Apart from that
the chemical constituents, who were
found effective can also be
synthetically prepared for better
yield and obtain a pharmacophore
which may be useful for drug
design.
Bisht A at el, 2021 [35] Cedrus deodara (Roxb. ex D.Don) G.Don: A Cedrus deodara is a medicinal tree
review of traditional use, phytochemical traditionally important for its use in
composition and pharmacology. the management of skin diseases,
microbial infections, joint disorders,
asthma, immunological disorders,
 kidney stones etc.
Arezoo Rastegari et al, Cedrus deodara: In Vivo Investigation of Burn The burn wound healing activity of
2023 [57] Wound Healing Properties. the methanol extract of
C. deodara wood was studied in a
burn wound model using an
ointment formulation. It was
perceived that the plant can be
considered in the development of
effective healing agents for treating
burns as desirable antioxidant and
antibacterial properties were
confirmed.
Shrestha A et al, Aloe Vera As Traditional Medicinal Plant: A Aloe vera is a traditional medicinal
2015 [32] Review On Its Active Constituents, Biological herb, which is safely and effectively
And Therapeutic Effects. used in the treatment numbers of
internal and external diseases.
Phytochemical constituents present
in this herb are beneficial for most
digestive problems, including
constipation, colitis, poor appetite,
irritable bowel syndrome, asthma,
diabetes, immune system
enhancement, peptic ulcers and
periodontal diseases
Sahebnasagh A et al, Successful Treatment of Acute Radiation A substantial number of patients
2017 [47] Proctitis with Aloe Vera: A Preliminary with radiation proctitis seem to
Randomized Controlled Clinical Trial. benefit from therapy with Aloe
vera 3% ointment.
Heggie S et al, A Phase III study on the efficacy of topical aloe Aqueous cream is superior to aloe
2022 [48] vera gel on irradiated breast tissue. vera gel in reducing the acute
radiation skin side effects of dry
desquamation and pain. A 98% aloe
vera gel may reduce erythema,
although the significance of this is
unclear.
Goel A et al, 2007 [36] Curcumin as ‘‘Curecumin’’: From kitchen to extensive research over the last half
clinic. century has made clear that most
chronic illnesses can only be cured
 by multi-targeted, as opposed to
mono-targeted, therapy and that
promiscuous targeting of a disease
cell's multiple bypass mechanisms is
a therapeutic virtue .
Kim J et al, 2016 [58] Therapeutic effect of topical application of curcumin exhibited beneficial
curcumin during treatment of radiation burns in a effects in radiation burns by
mini-pig model. postponing the onset and decreasing
the severity of radiation-induced
dermatitis in a piglet model. When
compared to the vehicle-treated
group, the curcumin-treated group
showed reduced expression of COX-
2 and NF-κB in irradiated skin.
Irradiation prolonged healing of
biopsy wounds in the exposed area,
but curcumin treatment stimulated
wound-healing.
de Macedo LM, Rosemary (Rosmarinus officinalis L., syn Salvia Rosemary extract contains a large
2020 [59] rosmarinus Spenn.) and Its Topical Applications: variety of bioactive molecules with
A Review. great therapeutic potential. Topical
administration strategies avoid first-
pass metabolism, releasing the drug
at the site of action and resulting in a
lower risk of side effects. This
strategy can be applied to improve
the properties of cosmetic products
(e.g., those that combat UV
exposure, aging, and cellulite),
owing to the anti-inflammatory
activity and free radical-scavenging
effects of Rosemary.
ROLE OF MEDICINAL PLANTS:

1. PUNARNAVA [31, 42]

Botanical Name: Boerhavia Diffusa

Family: Nyctaginaceae
Parts Used: Root
Phytoconstituents: Flavonoids, Terpenoids, Phenolic Compound, Alkaloid, Retenoid, Steroids, Glycoside.
Medicinal Uses:
Wound healing, Analgesic, Anti-inflammatory, Antioxidant, Antibacterial, Diuretic, Immunomodulator,
Antidiabetic, Antifungal
2. ALOE VERA [32, 33]

Botanical Name: Aloe barbadenensis miller

Family: Asphodelaceae (Liliaceae)

Parts Used: Leaf

 Phytoconstituents: Tannic acid, Alkaloids, Polysaccharide,Vitamin, Enzymes, Sterols, Amino acid,
Minerals.

Medicinal Uses: Wound Healing, Analgesic, Anti-inflammatory, Antiseptic, Antibacterial

3. DEODAR [34, 35]

Botanical Name: Cedrus deodar

Family: Pinaceae

Parts used: bark

Phytoconstituents: Terpenoids, Flavonoids, Sterols, Ligans

Medicinal Uses: Anti-inflammatory, insomnia, bronchitis, skin disease, leukoderma, ophthalmia

4. TURMERIC [36, 37, 38]

Botanical Name: Curcuma longa

Family: Zingiberaceae

Plant used: Root

 Phytoconstituents: Curcumin, Curcuminoids, Cymene, polyphenol compounds, Demethoxycurcumin

Medicinal Uses: Antioxidants, Anti-inflammatory, skin cancer, UTI, Wound healing

5. ROSEMARY [39, 40, 41]

Botanical Name: Rosmarinus officinale

Family: Lamiaceae

Parts Used: Dried leaves

Phytoconstituents: Terpenoids, Essential oils, Alkaloids, Flavonoids

Medicinal Uses:

As a preservatives, Increase Blood circulation, Cell growth, Anti-inflammatory, Regenerate cells

RATIONALE:

 The skin comes mind when we think of wounds.

 It is our primary external organ and both vulnerable to damage and capable of healing.
 A correct and efficient wound management is essential.
 Emphasis is requires on new and alternative therapeutic approaches and development of technologies for
acute and chronic wound healing.
 In traditional system of medicine, ointment is one of the oldest medicinal dosage forms, in order to integrate
two pharmaceutical elements with distinct therapeutic actions for a single target, ointment was formulated.
 Ointments which were applied topically for wounds and some swellings are a mixture of finely ground and
pulverised medications with beeswax, oils, animal fats, or bone marrow. It is said that beeswax aids in
maintaining the ointments consistency, which can stop the formulation from running and result in the
ointment’s long-term durability on the skin.
 Several drugs obtained from plant sources are known to increase the healing of different types of wounds.
Maximum wound healing activity studies performed so far are extracts of herbs individually. However,
 Polyherbal topical formulations with synergistic mechanism of action may become better approach in
treatment of wounds.
 Pharmaceutical ointment are therapeutic preparation that delivers medication to the affected areas on different
region of our Body.
 It can be used to treat swelling and burning skin of the Body.
 The formulation having key ingredient like Punarnava which mainly play important role in skin burning.
 The ointment of following ingredients are rarely available in market in combination form.
 This ointment formulation of following ingredients are available in individual form but not in combinational
form.

MECHANISM OF ACTION:

PUNARNAVA:

Additionally, the author extracted punarnava from the extract, which demonstrated complement-mediated
cytotoxicity and antibody-dependent cellular cytotoxicity in addition to NK cell activation increase. IFN-γ and IL-2
production were elevated by punarnava [44]. Punarnava treatment dramatically reduced levels of GM-CSF and
proinflammatory cytokines such IL-1α, IL-6, and TNF-α. Additionally, the author discovered that punarnava (40
mg/kg) administered prophylactically and concurrently can suppress lung melanoma metastasis up to 95.25%–93.9%,
respectively, for ten days following tumor inoculation. The treatment of punarnava likely inhibits or downregulates
the expression of VEGF, MMP-2, MMP-9, ERK-1, and ERK-2 in the lung tissue of animals that have been induced
to develop metastases [43, 55].

DEODAR [44] :

ROSEMARY:
Chronic skin inflammation, or atopic dermatitis, is typified by eczematous and itchy lesions that can be caused by
inflammatory cells, cytokines, and enzymes (e.g., COX-2, iNOS, and STAT3), among other things [45]. TNF-α and
IL-1β, two inflammatory cytokines, immunoglobulin E, and neutrophils in the blood were all found to be decreased
by rosemary [46, 59].

ALOE VERA:

Although the exact mechanism of action of aloe vera is unknown, inhibition of cyclooxygenase is thought to be
involved [47, 48]. Because aloe vera has antioxidants and anti-inflammatory qualities, it can help cure burns and
hasten the healing of wounds. One possible explanation for this is that it inhibits cyclooxygenase [47]. Aloe vera may
also have an effect on platelet and leukocyte aggregation, which results in less vasoconstriction and promotes wound
healing [49].
TURMERIC:

Researchers have discovered that curcumin, which can suppress the manufacture and activity of several enzymes
linked to inflammation, including cyclooxygenase-2 (COX2) and 5-lipooxygenase (5-LOX), is responsible for
turmeric's anti-inflammatory properties [50, 51, 58].

ROSEMARY ALOE VERA DEODAR TURMERIC

PUNARNAVA

Decrease TNF-α PARP GSH, SOD Cisplatin curcumin

GPx, se catalase Passive diffusion cox-2, Lox-2

Activate Endothelium Cleaved PARP CTR1 Anti-

Antioxident effect
inflammatory

& Granulocytes Hydrolysis Anticancer

Cox-2 PS3, JNK

Induce Tumor cell lox-5 DNA crosslink

G2/ M phase

AKT

m-TOR

cell proliferation

& survival

Cell
growth
 Necrosis &
Apoptosis

MATERIALS AND METHODS:

STEP-1: Simple Ointment formulation:

Simple ointment B.P. was prepared using hard paraffin, cetostearyl alcohol, white soft paraffin, and wool fat. The
master formula used for the preparation of ointment was taken from British Pharmacopoeia [52]. Since there will be
little wastage (loss) of ingredients during weighing and preparing, to manipulate these practical losses, calculate the
ingredients for atleast one or two grams extra, than prescribed.

1. Weigh all the ingredients according to calculation.

2. Melt Hard Paraffin and cetostearyl alcohol in a porcelain dish, by keeping on a water bath.
3. To this melt, incorporate wool fat and white soft paraffin, stir well during melting.
4. After melting of all ingredients, remove the foreign matter if present by decanting or straining into another hot
dish.
5. Stir the mixture thoroughly, until it becomes cooled and a semi-solid base is obtained.

INGREDIENTS QUANTITY GIVEN QUANTITY TAKEN

Wool fat 1.6 gm
Hard paraffin 1.6 gm
Cetostearyl alcohol 1.6 gm
White or Yellow soft paraffin 27.2 gm

STEP-2: AYURVEDIC OINTMENT FORMULATION:

1. Weigh all the ingredients according to calculation.

2. After weighing mix all ingredients.
3. Take sieve #120 to separating wanted elements from unwanted materials or for controlling particle size of a
sample. ( weign each ingredients 1-2 gm extra.)
4. This mixture of fine particles of ingredients is incorporated into the portion of simple ointment base to prepare
Ayurvedic Ointment.

INGREDIENTS QUANTITY ROLE OF INGREDIENTS

Punarnava Anti-inflammatory
Antiproliferative
Deodar Antiproliferative
Turmeric Antioxident
Anti-inflammatory
Aloe vera Cell Regenerative, Antiseptic
Anti-inflammatory

Rosemary Cell Regenerative, As a Preservative

[BATCH-1] [BATCH-2]

[BATCH-3]

CHEMICAL TESTS [53, 54, 57]

1. Tannic acid test:

Take pinch of sample in a test tube
 Add tannic acid reagent into sample containing test tube

Precipitate is obtain.

2. Fehling test:
Take a pinch of sample in a test tube

Add Feling A & Fehling B solution in sample containing test tube

Keep test tube containing mixture in water bath for 5-10 mins.

Yellow brick red color ppt is obtain.

3. Millon’s test:
Take a pinch of sample in a test tube

Add millon’s reagent into sample containing test tube

Heat the mixture in water bath for 2 mins

Brick red color ppt is obtain.

4. Ferric chloride test:

Take a pinch of sample in a test tube

Add millon’s reagent into sample containing test tube

Heat the mixture in water bath for 2 mins

Blackish bluish color is obtain.

5. Iodine test:
Take a pinch of sample in a test tube

Add iodine solution into sample containing test tube

Heat the mixture in water bath for 2 mins

Bluish color ppt is obtain.

METHOD OF DETERMINING EVALUATION PARAMETERS:

Evaluation of Polyherbal Formulation:-

The Polyherbal Formulation was evaluated by the following physicochemical parameters.

 1. Color and Odour
Color and odour was examined by visual examination.
2. Loss on Drying
Loss on drying was determined by placing the ointment in a petridish on a waterbath and dried until constant
weigh was obtained.
3. PH
The PH of formulation was recorded using a ph paper.
4. Spreadability
The spread ability was expressed in terms of times in seconds taken by two slides to slip off from ointment
placed in between the slides under the direction of certain load. Spread ability was calculated by using the
formula:
S = (M.L/T)
Where, S = Spreadability
M = Weight tied to upper slide
L = Length of glass slides and
T = Time taken to separate the slides.
5. Consistency:
Smooth and no greediness is observed.
6. Non-irritancy test:
Herbal ointment was applied to the skin of human being and observed for the effect.

RESULT:

The result of evaluation parameters are below:

 EVALUATION PARAMETERS:

PHYSICO-CHEMICAL PARAMETERS RESULT

COLOUR BROWNISH COLOUR

ODOUR
LOSS ON DRYING
PH 5
SPREADABILITY
 NON-IRRITANCY TEST

The result of chemical tests are as below:

 CHEMICAL TEST:

TEST RESULT
Tannic acid test STARCH PRESENT

Fehling test REDUCING SUGAR PRESENT

Millon’s test PROTEIN PRESENT

Ferric chloride test TANNINS PRESENT

Iodine test TANNINS PRESENT

CONCLUSION:

The formulation of the Ayurvedic skin ointment containing punarnava, deodar, aloe vera, turmeric, and rosemary
shows promising potential in providing relief and improving the skin health of chemotherapeutic patients. These
ingredients have been traditionally used in Ayurvedic medicine for their anti-inflammatory, antioxidant, and healing
properties, which are beneficial for treating skin conditions often experienced by cancer patients undergoing
chemotherapy. The evaluation of the ointment in terms of its safety, efficacy, and acceptability among patients can
provide valuable insights into its therapeutic value. Further clinical trials and studies are warranted to validate the
efficacy of this Ayurvedic ointment in improving the quality of life and well-being of chemotherapeutic patients.
REFERENCES:

1. Nicola Luigi Bragazzi, Maha Sellami, Iman Salem , Rosalynn Conic ,Mark Kimak ,Paolo Daniele Maria Pigatto
and Giovanni Damiani. Fasting and Its Impact on Skin Anatomy, Physiology, and Physiopathology: A
Comprehensive Review of the Literature. MDPI journal. Nutrients 2019, (11), 3-5

2. Paul A.J. Kolarsick, BS, Maria Ann Kolarsick, MSN, ARNP-C, and Carolyn Goodwin, APRN-BC, FNP Anatomy
Anatomy and Physiology of the Skin. Oncology Nursing Society. Available from: http://www.ons.org/

3. Maranduca MA, Branisteanu D, Serban DN, Branisteanu DC, Stoleriu G, Manolache N, Serban IL. Synthesis and
physiological implications of melanic pigments. Oncol Lett. 2019 May;17(5):4183-4187.

4. Someya T, Amagai M. Toward a new generation of smart skins. Nat Biotechnol. 2019 Apr;37(4):382-388.

5. Nicola Luigi Bragazzi, Maha Sellami , Iman Salem , Rosalynn Conic ,Mark Kimak ,Paolo Daniele Maria Pigatto
and Giovanni Damiani. Fasting and Its Impact on Skin Anatomy, Physiology, and Physiopathology: A
Comprehensive Review of the Literature. MDPI journal . Nutrients 2019, (11), 3-4.

6. WHO Burn fact sheets, 2018, https://www.who.int/news-room/fact-sheets/detail/burns.

7. M. Abazari, A. Ghaffari, H. Rashidzadeh, S. M. Badeleh, and Y. Maleki, “A systematic review on classification,

identification, and healing process of burn wound healing,” The International Journal of Lower Extremity Wounds,
vol. 21, no. 1, pp. 18–30, 2022.
View at: Publisher Site | Google Scholar

8. M. J. N. Chandrasekar, S. Ramalingam, and M. J. Nanjan, “Plant-based natural products for wound healing: a
critical review,” Current drug research reviews, vol. 14, no. 1, pp. 37–60, 2022.
View at: Publisher Site | Google Scholar

9. I. Adadi, R. E. Ayadi, A. Bentayeb et al., “Phytochemical profile, in vivo anti-inflammatory and wound healing
activities of the aqueous extract from aerial parts of Cistus ladanifer L,” Journal of Pharmaceutical and Biomedical
Analysis, vol. 219, Article ID 114960, 2022.
View at: Publisher Site | Google Scholar

10. S. Niknam, A. Rastegari, M. Bozorgi, Y. Vahedi-Mazdabadi, M. Saeedi, and T. Akbarzadeh, “Vivo evaluation of
wound healing properties of platanus orientalis L,” Pharmaceutical Sciences, vol. 28, no. 2, pp. 275–284, 2021.
View at: Google Scholar

11. N. Salhi, A. Bouyahya, A. Bounihi et al., “Investigation of wound healing activity Cynara humilis of root
extracts,” Journal of Cosmetic Dermatology, vol. 21, no. 4, pp. 1596–1609, 2022.
View at: Publisher Site | Google Scholar
12. S. Karakaya, I. Süntar, O. F. Yakinci et al., “In vivo bioactivity assessment on Epilobium species: a particular
focus on Epilobium angustifolium and its components on enzymes connected with the healing process,” Journal of
Ethnopharmacology, vol. 262, Article ID 113207, 2020. View at: Publisher Site | Google Scholar
13. M. Andjić, N. Draginić, A. Kočović et al., “Immortelle essential oil-based ointment improves wound healing in a
diabetic rat model,” Biomedicine & Pharmacotherapy, vol. 150, Article ID 112941, 2022.
View at: Publisher Site | Google Scholar

14. R. Samuelson, M. Lobl, S. Higgins, D. Clarey, and A. Wysong, “The effects of lavender essential oil on wound
healing: a review of the current evidence,” Journal of Alternative & Complementary Medicine, vol. 26, no. 8, pp.
680–690, 2020.
View at: Publisher Site | Google Scholar

15. M. T. B. Carvalho, H. G. Araújo-Filho, A. S. Barreto, L. J. Quintans-Júnior, J. S. S. Quintans, and R. S. S.

Barreto, “Wound healing properties of flavonoids: a systematic review highlighting the mechanisms of
action,” Phytomedicine, vol. 90, Article ID 153636, 2021.
View at: Publisher Site | Google Scholar

16. J. Fisher et al.

Randomized phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced
skin toxicity for women undergoing breast irradiation: radiation therapy oncology group (RTOG) 97-13
Int J Radiat Oncol Biol Phys (2000)

17. J.O. Archambeau et al.

Pathophysiology or irradiated skin and breast
Int J Radiat Oncol Biol Phys (1995)

18. I.R. Campbell et al.

Can patients wash during radiotherapy to the breast or chest wall? A randomised controlled trial
Clin Oncol (1992)

19. B.A. Lavery

Skin care during radiotherapy: a survey of UK practice
Clin Oncol(1995)

20. D.P. West et al.

Evaluation of aloe vera gel gloves in the treatment of dry skin associated with occupational exposure
Am J Infect Control (2003)

21. M.S. Williams et al.

Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity
Int J Radiat Oncol Biol Phys (1996)

22. Hoashi T, Okochi H, Kadono T, Tamaki K, Nishida M, Futami S, Maekawa K. A case of acute radiation
syndrome from the dermatological aspect. Br J Dermatol. 2008;158:597–602. [PubMed] [Google Scholar]

23. Hopewell JW. The skin: its structure and response to ionizing radiation. Int J Radiat Biol. 1990;57:751–
773. [PubMed] [Google Scholar]

24. Bernstein EF, Sullivan FJ, Mitchell JB, Salomon GD, Glatstein E. Biology of chronic radiation effect on tissues
and wound healing. Clin Plast Surg. 1993;20:435–453. [PubMed] [Google Scholar] [Ref list]
25. Denham JW, Hauer-Jensen M, Peters LJ. Is it time for a new formalism to categorize normal tissue radiation
injury? Int J Radiat Oncol Biol Phys. 2001;50:1105–1106. [PubMed] [Google Scholar] [Ref list]

26. Jagetia GC. Radioprotective potential of plants and herbs against the effects of ionizing radiation. J Clin Biochem
Nutr. 2007;40:74–81. [PMC free article] [PubMed] [Google Scholar] [Ref list]

27. Kim JS, Yang M, Kim SH, Shin T, Moon C. Neurobiological toxicity of radiation in hippocampal cells. Histol
Histopathol. 2013;28:301–310. [PubMed] [Google Scholar] [Ref list]

28. Kim JS, Yang M, Lee CG, Kim SD, Kim JK, Yang K. In vitro and in vivo protective effects of granulocyte
colony-stimulating factor against radiation-induced intestinal injury. Arch Pharm Res. 2013;36:1252–
1261. [PubMed] [Google Scholar] [Ref list]

29. Son TG, Gong EJ, Bae MJ, Kim SD, Heo K, Moon C, Yang K, Kim JS. Protective effect of genistein on
radiation-induced intestinal injury in tumor bearing mice. BMC Complement Altern Med. 2013;13:103. [PMC free
article] [PubMed] [Google Scholar] [Ref list]

30. Anand U, Dey A, Chandel AKS, Sanyal R, Mishra A, Pandey DK, De Falco V, Upadhyay A, Kandimalla R,
Chaudhary A, Dhanjal JK, Dewanjee S, Vallamkondu J, Pérez de la Lastra JM. Cancer chemotherapy and beyond:
Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2022 Mar
18;10(4):1367-140

31. Rao P, Pundareekaksha P, Assistant R, Rao PP. Essential Leafy Vegetables for Healthy Eyes. International
Journal of Herbal Medicine [Internet]. 2016 [cited 2022 Feb 15];4(6):120–3. Available from:
https://www.researchgate.net/publication/335389783

32. Shrestha A, Acharya A, Nagalakshmi NC. Aloe Vera As Traditional Medicinal Plant: A Review On Its Active
Constituents, Biological And Therapeutic Effects. World Journal Of Pharm. Research. 2015 Apr 15; 4:2146-61.

33. Davis RH, Leitner MG, Russo JM, Byrne ME. Wound Healing. Oral And Topical Activity Of Aloe Vera. J Am
Podiatr Med Assoc. 1989 Nov 1;79(11):559-62.

34. A review on ethnobotanical, phytochemical and pharmacological … [Internet]. [cited 2022Dec15]. Available
from: http://www.iscientific.org/wp-content/uploads/2019/09/6-IJCBS-19-15-6.pdf

35. Bisht A, Jain S, Misra A, Dwivedi J, Paliwal S, Sharma S. Cedrus deodara (Roxb. ex D.Don) G.Don: A review of
traditional use, phytochemical composition and pharmacology. Journal of Ethnopharmacology. 2021
Oct;279:114361. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0378874121005900?via
%3Dihub

36. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as ‘‘Curecumin’’: From kitchen to clinic. Biochemical
Pharmacology. 2008; 75(4):787-809. Epub 2007 Aug 19

37. Tieraona Low Dog. A Reason to Season: The Therapeutic Benefits of Spices and Culinary Herbs. Explore: The
Journal of Science and Healing. 2006; 2(5): 446 -449.

38. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med
Biol. 2007; 595:453-70.

39. Knupp K, Parsons J. Nervous system disorders. In: Feldman HM, editor. Developmental-behavioral
pediatrics. 4th ed. Philadelphia: Saunders; 2009. pp. 213–223. [Google Scholar]

40. Li JW, Vederas JC. Drug discovery and natural products: end of an era or an endless
frontier? Science. 2009;325:161–165. [PubMed] [Google Scholar]
41. Boyd A, Bleakley C, Gill C, McDonough S, Hurley DA, Bell P, McVeigh JG, Hannon- Fletcher M. Herbal
medicinal products or preparations for neuropathic pain and fibromyalgia. Cochrane Database Syst
Rev. 2013;5:CD010528. [PMC free article] [PubMed] [Google Scholar]

42. Bihari Dora B, Dora BB, Gupta S, Sital S, Pastore A. Punarnava (Boerhavia diffusa): A Promising Indigenous
Herbal Drug and Its Effect on Different Disease Conditions. 2015 [cited 2022 Feb 15];21–4.

43. K. A. Manu and G. Kuttan, “Anti-metastatic potential of Punarnavine, an alkaloid from Boerhaavia diffusa
Linn,” Immunobiology, vol. 214, no. 4, pp. 245–255, 2009.
View at: Publisher Site | Google Scholar

44. P. B. Comish, D. Carlson, R. Kang, and D. Tang, J. Immunol. 205 (5), 1189 (2020).
https://doi.org/10.4049/2000439/jimmunol
45. Lim, S.J.; Kim, M.; Randy, A.; Nam, E.J.; Nho, C.W. Effects of Hovenia dulcis Thunb. extract and methyl
vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells. J.
Pharm. Pharmacol. 2016, 68, 1465–1479. [Google Scholar] [CrossRef]

46. Lee, D.Y.; Hwang, C.J.; Choi, J.Y.; Park, M.H.; Song, M.J.; Oh, K.W.; Son, D.J.; Lee, S.H.; Han, S.B.; Hong,
J.T. Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of
STAT3. Biomol. Ther. 2017, 25, 535–544. [Google Scholar] [CrossRef] [PubMed] [Green Version]

47. Sahebnasagh A, Ghasemi A, Akbari J, Alipour A, Lashkardoost H, Ala S, Salehifar E. Successful Treatment of
Acute Radiation Proctitis with Aloe Vera: A Preliminary Randomized Controlled Clinical Trial. J Altern
Complement Med. 2017 Nov;23(11):858-865. doi: 10.1089/acm.2017.0047. Epub 2017 Jun 15. PubMed PMID:
28618234.

48. Heggie S, Bryant GP, Tripcony L, Keller J, Rose P, Glendenning M, Heath J. A Phase III study on the efficacy of
topical aloe vera gel on irradiated breast tissue. Cancer Nurs. 2002 Dec;25(6):442-51. PubMed PMID: 12464836.

49. Yagi A, Kabash A, Mizuno K, Moustafa SM, Khalifa TI, Tsuji H. Radical scavenging glycoprotein inhibiting
cyclooxygenase-2 and thromboxane A2 synthase from aloe vera gel. Planta Med. 2003 Mar;69(3):269-71. PubMed
PMID: 12677534.

50. Tieraona Low Dog. A Reason to Season: The Therapeutic Benefits of Spices and Culinary Herbs. Explore: The
Journal of Science and Healing. 2006; 2(5): 446 -449.

51. Sharma RA, Steward WP, Gescher AJ. Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med
Biol. 2007; 595:453-70
52. British Pharmacopoeia (BP). Department of health and social security Scottish home and health department.
Office of the British Pharmacopoeia Commission, UK, vol. 2, pp. 713, 1988. [CrossRef] [Ref list]

53. Dr. K.R.Khendelwal, Dr. Vrunda Sethi “Practical pharmacognosy techniques and experiments”,27th edition,
Nirali Prakashan,2016, pg no: 25.1- 25.3 2.

54. Biren Shah, B.S.Nayak “Experimental pharmacognosy” 1st edition, s. vikas publication, 2009 pg no: 190- 194

55. Shikha Mishra, Vidhu Aeri, Praveen Kumar Gaur, Sanjay M. Jachak, "Phytochemical, Therapeutic, and
Ethnopharmacological Overview for a Traditionally Important Herb: Boerhavia diffusa Linn.", BioMed Research
International, vol. 2014, Article ID 808302, 19 pages, 2014. https://doi.org/10.1155/2014/808302

56. Mahesh AR, Kumar H, Ranganath MK, Devkar RA. Detail study on Boerhaavia diffusa plant for its medicinal
importance-A Review. Res J Pharm Sci. 2012 Sep;1(1):28-36.
57. Arezoo Rastegari, Azadeh Manayi, Tahmineh Akbarzadeh, Reza Hojjatifard, Nasrin Samadi, Mahnaz Khanavi,
Somayeh Niknam, Mina Saeedi, "Cedrus deodara: In Vivo Investigation of Burn Wound Healing
Properties", Evidence-Based Complementary and Alternative Medicine, vol. 2023, Article ID 5596964, 8 pages,
2023. https://doi.org/10.1155/2023/5596964

58. Kim J, Park S, Jeon BS, Jang WS, Lee SJ, Son Y, Rhim KJ, Lee SI, Lee SS. Therapeutic effect of topical
application of curcumin during treatment of radiation burns in a mini-pig model. J Vet Sci. 2016 Dec 30;17(4):435-
444.
59. de Macedo LM, Santos ÉMD, Militão L, Tundisi LL, Ataide JA, Souto EB, Mazzola PG. Rosemary (Rosmarinus
officinalis L., syn Salvia rosmarinus Spenn.) and Its Topical Applications: A Review. Plants (Basel). 2020 May
21;9(5):651. doi: 10.3390/plants9050651. PMID: 32455585; PMCID: PMC7284349.