1. Introduction

nkle injuries are one of the most common musculoskeletal injuries in sports activities, which generally account for 10-15% of all injuries. The ankle is a joint in which the tibia bones and fibula at the bottom of the leg and the talus bone at the top of the calcaneus (heel bone) meet to support the weight of the body.

In a study by Khan et al. (2010), the induction of acute inflammation in rats and the subsequent use of the methanolic extract of Chelleh Daghi plant at a dose of 300 mg/kg showed high anti-inflammatory effects [6, 7].

Eremostachys laevigata (known as Chelleh Daghi in Iran) belongs to the genus Eremostachys and the Lamiaceae family. The genus Eremostachys, called Sonbol-e-Biyabani in Persian, includes about 60 species. It is necessary to conduct comprehensive research to identify its therapeutic properties. Since controlling pain and inflammation in ankle sprains is one of the main goals of treatment and previous studies have shown the anti-inflammatory and analgesic effects of Chelleh Daghi plant, so we decided to compare the topical form of this plant called Chelleh Daghi ointment with a common therapeutic gel such as Piroxicam.

2. Materials and Methods 

This study was performed as a double-blind clinical trial by sequential sampling method for 6 months from August 2018 to January 2019. After referral, all patients completed the consent form. Then, the patients' characteristics and study variables were recorded by an evaluator in the research form. Patients received their standard treatments, but the type of ointments was not the same. According to their referral, the patients were randomly divided into two groups of “treatment with piroxicam gel” and “treatment with Chelleh Daghi ointment”. 

In the control group, piroxicam gel was used twice a day for 3 weeks and 3-5 grams each time. In the intervention group, Chelleh Daghi ointment was used twice a day for 3 weeks and 3-5 grams each time. Patients' pain intensity was assessed by the Visual Analogue Scale (VAS), which used a 100 mm horizontal line without a number. At the left end of this line, the point “painless” and at the right end, the point “very severe pain” was designated.

In the first session (before starting the treatment), and then in the second and third sessions of the treatment, the patients were asked to mark the severity of their pain on the aforementioned line. Symptoms of ankle ecchymosis were also assessed through physical examination and observation and recorded in a checklist [15, 16]. After collecting and entering the data in SPSS V. 18 software, statistical analysis was performed using statistical tests (Chi-square, Mann-Whitney U, and one-way ANOVA ).

3. Results

According to the results, the Mean±SD of age was 35.4±8.9 years in the Chelleh Daghi Ointment group, and 34.2±8.6 years in the Piroxicam Gel group.

The Mean±SD of height was 1.72±0.11 m in the Chelleh Daghi ointment group and 1.7±0.12 m in the Piroxicam Gel group. The Mean±SD of weight was 82.9±13.3 kg in the Chelleh Daghi ointment group and 82.1±15.0 kg in the piroxicam gel group. The Mean±SD of the number of days of use was 13.1±9.0  in the Chelleh Daghi ointment group and 12.4±9.3 in the piroxicam gel group. There was no statistically significant difference in “weight” and “number of days of use” between the two groups (P>0.05). In the Chelleh Daghi ointment group, there were 26 (43%) male patients and 5 (8%) female patients. In the piroxicam gel group, there were 25 (42%) male patients and 4 (7%) female patients. According to the chi-square test, the frequency distribution was identical in the two groups (P>0.05). 

The Mean±SD of pain the intensity in the Chelleh Daghi ointment group was 9±0.4 before the intervention and 3.2±2.1 after the intervention, and in the piroxicam gel group, it was 9.8±0.3 before the intervention, and 7.4±1.5 after the intervention. According to the Wilcoxon test, there was a statistically significant difference between the mean pain intensity in the Chelleh Daghi ointment group (P<0.05), but in the piroxicam gel group the difference was not significant (P>0.05).

Based on the ANCOVA test, there was a statistically significant difference between the mean pain intensity before and after the intervention in both Chelleh Daghi ointment and piroxicam gel groups (P<0.5).

The Mean±SD of intensity of inflammation in the Chelleh Daghi ointment group was 9±1.8 before the intervention and 1.2±0.9 after the intervention, and in the piroxicam gel group it was 9.05±1.8 before the intervention and 3.1±1.9 after the intervention. According to Wilcoxon test, there was a statistically significant difference between the mean inflammation intensity in the Chelleh Daghi ointment group and the piroxicam gel group (P<0.05).

According to the Mann-Whitney U test, before the intervention, there were no statistically significant difference between the mean pain intensity in the two (Chelleh Daghi ointment and piroxicam gel) groups (P>0.05), but after the intervention, there was a statistically significant difference (P<0.05). According to the ANCOVA test, there was a statistically significant difference between the mean pain intensity in the two (Chelleh Daghi ointment and piroxicam gel) groups before and after the intervention (P<0.5).

According to the Chi-square test (Fisher’s method), it was found that the frequency distribution of “ecchymosis” in the two (Chelleh Daghi ointment and piroxicam gel) groups were not identical (P>0.05), and the frequency distribution of “inflammation around the joint” in both Chelleh Daghi ointment and piroxicam gel groups was identical (P<0.05).

4. Discussion and Conclusion

In traditional medicine, the glandular roots of the Chelleh Daghi plant are used topically to relieve inflammation and pain in musculoskeletal disorders, which may be due to the anti-inflammatory and analgesic properties of the plant [17, 18]. The results of this study showed that the average rate of the pain in the Chelleh Daghi ointment group was significantly reduced compared to the piroxicam gel group (P<0.05); also, the average rate of the severity of inflammation in both Chelleh Daghi ointment and piroxicam gel groups was significantly lower than before using of both ointments. In addition, there was a significant difference between the average rate of the severity of inflammation in the Chelleh Daghi group compared to the piroxicam gel group (P<0.05). 

The results of the study on the effect of Chelleh Daghi and piroxicam gel on the indicators of ecchymosis and joint inflammation showed that the Chelleh Daghi plant significantly reduce joint inflammation after using this ointment (P<0.05). Also, regarding the effect of Chelleh Daghi ointment on ecchymosis, the results showed a decrease in ecchymosis after using the ointment, but this reduction was not statistically significant (P>0.05).

The results of new trials showed that using the new analgesics increases inflammation and cardiovascular problems, and older types of these drugs cause gastrointestinal problems. One study found that commonly prescribed Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) inhibited the matrix synthesis of cartilage in humans, which in turn increased the cartilage destruction of joints in osteoarthritis. Therefore, many researchers are looking for a drug that is effective and causes fewer side effects. Our results in this study showed that the use of Chelleh Daghi ointment compared to piroxicam ointment has far better effects in relieving pain. Some other studies also showed that no side effects such as nausea, which was observed in piroxicam, were not observed in Chelleh Daghi. Using Chelleh Daghi ointment for 3 weeks can be more effective than piroxicam gel in reducing the severity of ankle sprains. 

Ethical Considerations

Compliance with ethical guidelines

The Research Ethics Committee of Arak University of Medical Sciences approved the study (Code: IR.ARAKMU.REC.1396.55) and registered by the Clinical Trial (Code: IRCT2017071720258N53).

Funding

This research was supported by Arak University of Medical Sciences Vice Chancellor for Research and Behvarzan Pharmaceutical Company.

Authors' contributions

Data collection: Alireza Amani; Methodology: Ali Kamali; Writing – review & editing: Bahman Sadeghi and Ali Reza Sistani; Preparation of herbal ointment: Sajad Ghodibigi, Mahdi Tavakolizadeh and Farid Saghabi; Data analysis: Mojtaba Ahmadlou. 

Conflicts of interest

The authors state that there is no conflict of interest.

Acknowledgements

The authors of this research project would like to appreciate the patients for their patience and supports. We also appreciate Vice-Chancellor for Research of Arak University of Medical Sciences and Behvarzan Pharmaceutical Company for their helpful contribution and financial support.