*2.3.2. Marham-e-Ral*

Similarly, a study described the wound healing effect of a Unani formulation *Marham-e-Ral* in rats. Ingredients of this formulation are *Shorea robusta Gaertn* (*Ral*), Camphor (*Kafoor*), Catechu (*Katha*), *Roghan-e-Gao*, and Beeswax. *Marham-e-Ral* was administered topically once a day till complete epithelialization occurred. Wound contraction and epithelialization were measured. Both excision and incision wound models were developed. Rate of wound contraction was significantly enhanced so was the epithelialization period. The plant ex‐ tracts have revealed presence of flavonoids, triterpenoids, and tannins which are known to contribute to wound healing. They also possess astringent, antimicrobial and antiinflamma‐ tory effects. Based on their study, the authors claimed the prohealing stroke *Marham-e-Ral* possesses [68].

### *2.3.3. Aloe (Elva)*

*Aloe* is one of the oldest plants documented across the globe and also features in Unani system of medicine where it is called as *'Elva'*. Oryan *et al*. [69] reported the detailed account of wound healing activity of *A*. *vera* in rats. They demonstrated that the wound healing was 50% faster with aqueous extract of *A*. *vera* as compared to silver sulfadiazine in case of open wounds.

### *2.3.4. Golnar-e-farsi*

*Punica granatum* (*Linn*.), known as *Golnar-e-farsi* in Iran, popularly known as pomegranate flowers and *Achillea kellalensis* (*Bioss*.) and *Hausskn* a well known traditional herb used in tribal medicine of Iran is locally known as *Golberrenjas or Bumadaran-e-Sabzekoh* were studied scientifically by Pirbalouti *et al*. in 2010. The authors reported their significant wound healing properties in rat excision wound model owing to their increased wound contraction ability and collagen turnover [70].

### *2.3.5. Shorea robusta*

**2.3. Unani medicines**

*2.3.2. Marham-e-Ral*

possesses [68].

*2.3.3. Aloe (Elva)*

*2.3.4. Golnar-e-farsi*

and collagen turnover [70].

*2.3.1. Iranian wound healing plants*

470 Wound Healing - New insights into Ancient Challenges

traditional wound healing use of the above plants [67].

Unani system of medicine has its origin in Iran and also has documented evidences of anti‐ microbial herbs possessing wound healing properties. Like Siddha, Unani system too has a mention of cow's ghee (*Roghan-e-gao*), *Shorea robusta*, etc. Following are examples of wound

Pirbalouti *et al*. reported the wound healing properties of five traditional Iranian plants on alloxan‐induced diabetic wounds in rats. Wound area, epithelialization time, and histopatho‐ logical characteristics were studied upon treatment with *Malva sylvestris*, *Punica granatum*, *Amygdalus communis*, *Arnebia euchroma*, *and Scrophularia deserti*. The results corroborated the

Similarly, a study described the wound healing effect of a Unani formulation *Marham-e-Ral* in rats. Ingredients of this formulation are *Shorea robusta Gaertn* (*Ral*), Camphor (*Kafoor*), Catechu (*Katha*), *Roghan-e-Gao*, and Beeswax. *Marham-e-Ral* was administered topically once a day till complete epithelialization occurred. Wound contraction and epithelialization were measured. Both excision and incision wound models were developed. Rate of wound contraction was significantly enhanced so was the epithelialization period. The plant ex‐ tracts have revealed presence of flavonoids, triterpenoids, and tannins which are known to contribute to wound healing. They also possess astringent, antimicrobial and antiinflamma‐ tory effects. Based on their study, the authors claimed the prohealing stroke *Marham-e-Ral*

*Aloe* is one of the oldest plants documented across the globe and also features in Unani system of medicine where it is called as *'Elva'*. Oryan *et al*. [69] reported the detailed account of wound healing activity of *A*. *vera* in rats. They demonstrated that the wound healing was 50% faster with aqueous extract of *A*. *vera* as compared to silver sulfadiazine in case of open wounds.

*Punica granatum* (*Linn*.), known as *Golnar-e-farsi* in Iran, popularly known as pomegranate flowers and *Achillea kellalensis* (*Bioss*.) and *Hausskn* a well known traditional herb used in tribal medicine of Iran is locally known as *Golberrenjas or Bumadaran-e-Sabzekoh* were studied scientifically by Pirbalouti *et al*. in 2010. The authors reported their significant wound healing properties in rat excision wound model owing to their increased wound contraction ability

healing plants or medicines (*marham*) according to Unani system of medicine.

*Shorea robusta* finds a mention in both Siddha and Unani systems of medicine. A study carried out by Wani *et al*. in 2011 reported the wound healing property of *S*. *robusta Gaertn*. *f*. in excisional and incisional wound models in rats. The ethanolic extract was found to accelerate wound contraction, increased tensile strength, and hydroxyproline content thus acting as a wound healer [71].

### **2.4. Chinese herbs**

As are Ayurveda and Siddha to India and Unani to Iran, traditional Chinese system of medicine has been practiced for ages in China. Traditional Chinese Medicine (TCM) focuses on the concept of Yin and Yang which describes two opposing yet complementary aspects of any one phenomenon. Yin is associated with poor circulation and healing and stagnation, while Yang is related with being overheated and excess of scar tissue. Thus for optimum wound healing, an ideal balance needs to be struck between Yin and Yang. Raw Chinese formulas are created specific to each patient. A raw formula means simply that the herbs in the formula are in their natural state without modification. Traditionally, raw Chinese formulas are given in their organic form, cooked for several hours, and then ingested, but it tends to have an undesirable taste. However, with wound healing, a topical application is convenient, effective, and has no or less side effects. Herbs can be utilized in their natural state and with their maximum potency. Few of the examples of wound healer herbs of TCM are as follows:


excessive deposition of collagen and also promoted collagen maturity, thus obstructing the formation of scar. The mechanism of the effect of ANBP on collagen expression is different in the early and late stages of wound healing, which is favourable for wound closure and scar contraction. Using proteomics approach, the authors suggested that ANBP promoted wound healing and condensed scarring by bidirectional regulation of the Transforming Growth Factor β (TGF‐ β)‐/Smad‐dependent pathway.


### **2.5. Ozone therapy**

Ozone therapy dates back to the year 1914 when it was used during World War I for the treatment of gas gangrene. Ozone has multiple therapeutic effects in wound healing due to the property of releasing nascent oxygen, which has been shown to have bactericidal capabil‐ ities and to stimulate antioxidant enzymes. There are few randomized clinical trials to verify the use of ozone therapy in the early stages of wound healing. To verify the same, Zhang *et al*. [78] recently carried out a study assessing the use of ozone therapy in the early stages of diabetic foot ulcer by estimating the expression of VEGF, TGF‐β, and Platelet derived growth factor (PDGF). The authors claimed that the oxygen‐ozone therapy increased the levels of all the above three endogenous growth factors which contributed to its enhanced wound healing ability. Similarly, Wainstain *et al*. [79] demonstarted that oxygen–ozone therapy along with conventional therapy for 24 weeks hastened the healing of diabetic foot ulcer. The theory that ozonated oil has wound healing property was investigated at our laboratory in an excision wound model using Sprague Dawley rats. The animals were divided into four groups, which were treated with sesame oil (vehicle), framycetin (standard), or two doses of ozonated sesame oil (peroxide values 500 and 700 mEq/1000 g, respectively). The formulations were topically applied on the excision wounds once daily for 11 consecutive days, and the animals were euthanized on the 12th day. Ozonated oil treated wounds had significantly higher tensile strength, collagen content, and superoxide dismutase activity than that of the vehicle treated wounds. Histopathological analysis of skin of the excised wound area treated with ozonated oil revealed better healing activity in comparison with the vehicle‐treated wounds. Thus it was concluded that ozonated oil can be of potential remedial use for healing wounds [80]. Another animal study was carried out by Kim *et al.* [81] to evaluate the therapeutic effects of ozonated olive oil in guinea pigs in acute cutaneous wound healing model. Full thickness punch wound was created on the back of guinea pigs and ozonated olive oil treatment was compared with pure olive oil and no treatment control group. The immunohistopathological results demon‐ strated that topical application of ozonated olive oil increased the levels of VEGF, TGF‐β, and PDGF thus accelerating acute cutaneous wound healing. A study conducted by Travagli *et al*. [82] reported a deleterious effect of ozone treatment on aged mice. The authors claimed that ozone therapy in 8‐week mice enhanced wound healing, while when administered to 18‐week mice, the full thickness excisional wound displayed delayed healing. This may also be attributed to reduced bacterial infection and/or increased O2 tension by O3 contact in wound area in younger population.
