CHAMOMILE AND WOUND HEALING

Wound healing occurs through four phases: hemostasis, inflammation, proliferation, and remodeling� For a wound to heal successfully, all four phases must occur in the proper sequence and time (Guo and DiPietro 2010)� The complete healing response was summarized by Flynn and Rovee (1982) as follows:

• Platelet aggregation at the site of injury followed by blood clotting to arrest bleeding�

• An inflammatory response with the infiltration of the leukocytes and asso-ciated inflammatory mechanisms at the site of injury� The neutrophils move in and begin the process of phagocytosis to remove damaged cells, foreign matter, and bacteria� Then the macrophages come in and release growth factors and cytokines�

• Fibroblast accumulation with enhanced collagen synthesis at the injury site�

• Epithelial cell migration, division, and differentiation�

• Contraction of the wound, scarring, and remodeling of the scar�

This is a highly ordered process that occurs naturally� However, in pathological conditions, such as severe infection or ulcers, the process becomes disorderly� The inflammatory process becomes chronic with the presence of excessive neutrophils and ROS at the injury site� Sometimes there is an excessive deposition of collagen matrix leading to fibrosis (Diegelmann and Evans 2004)�

3.5.1 woUnd healinGand UlCer-proteCtive propertyof Chamomile

Chamomile extracts and oil have been found to have ulcer-protective capabilities�

The active compound appears to be (−)-α-bisabolol�

3.5.1.1 Chamomile Extract

Presibella et al� (2006, 2007) studied the effect of chamomile extracts on human leu-kocyte chemotaxis� Leuleu-kocytes were extracted and a 1% casein gradient was used

for leukocyte migration in a Boyden system� The effect of different concentrations of chamomile extract (0�1–10³μg/mL) was tested on leukocyte migration� Dexamethasone was used as the standard drug� It was found that chamomile extracts (0�1–10 μg/mL) significantly reduced the leukocyte migration� Presibella et al� concluded that by inhibiting leukocyte migration during inflammation of injury sites, chamomile could alleviate the symptoms of inflammation and improve wound healing�

Karbalay-Doust and Noorafshan (2009) carried out a study to explore the anti-ulcerogenic effect of chamomile extract in Balb/c mice� The mice were pretreated with 400 mg/kg extract and then gastric ulceration was induced� After 14 days the gastric lesions were measured� It was found that chamomile extract prevented gastric ulceration�

The effect of chamomile extract on wound healing was also studied by Jarrahi et al� (2010)� Wistar rats were subjected to linear wounds on the skin of the back�

Chamomile extract dissolved in olive oil was applied and significant improvement in wound healing was observed indicating that chamomile extract applied topically has wound healing potential�

Cemek et al� (2010) studied the effect of chamomile hydroalcoholic extracts on ethanol-induced gastric mucosal injury in rats� During the experiment, rats were pretreated with different doses of chamomile extract and then were induced with gastric mucosal injury using ethanol� It was found that chamomile extract signifi-cantly reduced gastric lesions and malondialdehyde levels� It was also found that the glutathione, serum β-carotene, and retinol levels were significantly higher in rats that were administered 200 mg/kg chamomile extract� The researchers concluded that the gastroprotective effect was due to the reduction in lipid peroxidation and also due to the augmentation in antioxidant activity�

Aqueous extracts of chamomile studied by Pizarro Espín et al� (2012) were found to have gastroprotective properties in Sprague Dawley rats� Indomethacin (50 mg/kg) was used to induce ulcer in the rats, ranitidine (100 mg/kg) was used as a positive control, and distilled water was used as negative control� The aqueous extracts of chamomile at doses 125, 250, and 500 mg/kg were administered to the rats� Chamomile at all the doses showed gastroprotective activity but the most effec-tive doses were 250 and 500 mg/kg�

Zaidi et al� (2012) studied the anti-inflammatory and cryoprotective effects of chamomile extracts on Helicobacter pylori-infected gastric epithelial cells� They also investigated the secretion of IL-8 and the presence of ROS in these cells� They found that chamomile did not significantly affect IL-8 secretion, but its effect was significantly high in aiding ROS generation� They concluded that this result demon-strated the potential of chamomile as a candidate drug for chemoprevention against peptic ulcer or gastric ulcer�

3.5.1.2 (−)-α-Bisabolol

The studies on the wound healing effect of (−)-α-bisabolol were reviewed by Isaac (1979)� In this review, he reported that in guinea pigs exposed to UV light, treatment with (−)-α-bisabolol led to a decrease in the skin temperature� In cutaneous burns of guinea pigs, there was a significant shortening of the healing time� (−)-α-Bisabolol was found to promote epithelization and granulation�

Szelenyi et al� (1979) studied the ulcer-protective effect of chamomile� Albino rats (190–250 g) were starved for 48 hours� Ulceration was caused by 20 mg/kg indomethacin in 1% methyl cellulose or by ethanol� Metiamid was used as control�

Different concentrations of bisabolol were administered orally followed 1 hour later by indomethacin� This was repeated for 3 days� The extent of ulcer inhibition was estimated according to ulcer index given by Munchow� The healing properties of the tested substance were measured comparatively with control and expressed in percentage� (−)-α-Bisabolol was found to inhibit indomethacin- or ethanol-induced ulcerations at ED₅₀= 145 mg/kg as compared to ED50= 595 mg/kg of metiamid�

Bezerra et al� (2009) studied the effect of chamomile and α-bisabolol against acute gastric lesions induced by absolute ethanol in rats� They also studied the role of pros-taglandins, NO, and K_ATP⁺ channels in the mechanism of gastroprotection induced by α-bisabolol� They found that chamomile reduced the gastric lesions� α-Bisabolol (50 and 100 mg/kg) significantly reduced the lesions� Further, they found α-bisabolol was effective even after pretreatment with N-nitro-l-arginine methyl ester (10 mg/kg), a NO antagonist, and indomethacin, an inhibitor of COX� When the rats were pretreated with glibenclamide, an inhibitor of K_ATP⁺ channel activation, the effect of α-bisabolol was significantly reduced� This led the researchers to conclude that α-bisabolol reduces gastric damage by the activation of K_ATP⁺ channels�

The effect of α-bisabolol on acute gastric mucosal lesions in mice was studied by Rocha et al� (2010)� They induced gastric ulcers in mice using ethanol and indometh-acin� Different concentrations of α-bisabolol of 100 and 200 mg/kg were adminis-tered to the mice� The results revealed that α-bisabolol was able to heal and protect the gastric mucosa from ulcer� Administration of Ofl-NAME, glibenclamide, or indomethacin on rats treated with α-bisabolol (200 mg/kg) was not able to revert the gastroprotection� In addition, it was observed that ethanol and indomethacin treat-ment had decreased the levels of nonprotein sulfhydryl groups whereas α-bisabolol had decreased the reduction of these sulfhydryl groups� This observation suggested an increase in the bioavailability of gastric sulfhydryl groups through α-bisabolol activity leading to a reduction of gastric oxidative injury induced by ethanol and indomethacin�

3.5.1.3 Chamomile Oil

Rezaie et al� (2012) carried out a comparative study to assess chamomile and zinc oxide on healing of skin wounds in rats� Incisional wound was made on Wistar rats and these were treated with two different concentrations of chamomile oil (10%

and 20%)� It was found that the 10% concentration of chamomile oil has significant wound healing properties�

3.5.1.4 Others

The wound healing potential of chamomile was also examined in farm animals�

Ahmad et al� (1995) took farm animals and two wounds were made on each ani-mal� One wound served as a control� To the other wound, chamomile lotion and ointment were applied topically and clinical, histopathological, histochemical, and microbial studies were carried out� They reported that quick healing was observed with chamomile lotion�

Langhorst et al� (2013) reported that in a clinical trial, they found that a herbal mixture containing chamomile was extremely safe and effective in the treatment of ulcerative colitis�