Evaluation of the Efficacy of Mobility Plus® in the Management of Osteoarthritis and Joint Inflammation in Canines

Osteoarthritis is a type of joint inflammation caused by the crumbling of the joint ligament. It is exceptionally common in most overweight canines and large breed canines (Aragon et al., 2007; Paster et al., 2005; Smith et al., 2006). Some breeds, such as Labrador Retriever and German Shepherd are even hereditarily inclined to have joint inflammation (Anderson et al., 2018). Osteoarthritis is accompanied by chronic pain, lameness and stiffness, particularly after prolonged activity. Their quality of life is reduced, leading to the loss of joint functions and mobility.
       
At present, there are no fixed treatments and the pharmacological treatment is restricted to the amelioration of clinical signs. Thus, the remedial administration for osteoarthritis in canines is overwhelmed by nonsteroidal anti-inflammatory drugs (NSAIDs), which are just ready to treat the manifestations of osteoarthritis by diminishing the pain and inflammation (Curry et al., 2005; Innes et al., 2003). In any case, the utilisation of NSAIDs might be related to hindering impacts, particularly gastrointestinal unfavourable impacts (Buttgereit et al., 2001). Other than pain relief, forestalling the ligament debasement is a significant goal for treatment and requires the long-term utilisation of safe modalities. Indeed, the absence of any cure reinforces the importance of prevention (Innes et al., 2003).
       
For these reasons, alternative treatments for canine osteoarthritis are desirable. Recently, nutraceuticals have been proposed for this purpose (Innes et al., 2003; Colitti et al., 2012; Henrotin et al., 2005). In addition, some herbal medicinal products have been shown to interact with the mediators of inflammation and therefore may be used to treat osteoarthritis (Cameron et al., 2009). These products can also act as free radicals through other mechanisms. However, up to now, few clinical trials have been carried out to substantiate the efficacy of herbal medicinal products.
       
With this scenario and the growing acceptance of traditional herbal preparations, the poly-herbal formulation Mobility Plus® was developed by Himalaya Wellness Company (Bengaluru, India). Mobility Plus® claims to possess antiarthritic, anti-inflammatory and analgesic activities in dogs. Hence, this study assessed the in vivo efficacy of Mobility Plus® in managing osteoarthritis and joint inflammation in dogs.

Poly-herbal formulation
 
Mobility Plus® is a proprietary poly-herbal formulation developed by Himalaya Wellness Company. It is composed mainly of shunti (Zingiber officinale), lasuna (Allium sativum), avocado (Persea americana), soybean (Glycine max), ananas (Ananas comosus) and guggul (Commiphora wightii).
 
Ethical committee approval
 
This study was conducted according to the guidelines for the care and use of animals. The study protocol was approved by the Institutional Animal Ethics Committee, Himalaya Wellness Company, Protocol No. AHP/SA/10/18 Institutional Ethics Committee.
 
Study subjects
 
A total of 18 client-owned dogs with a history of joint inflammation, hip dysplasia and arthritis, presented at Ganesh Pet Clinic, Bengaluru, Karnataka, India, were enrolled in the study. The study was conducted for the period of eight months from October 2018 to May 2019. The study details, treatment plan, outcomes and pros and consequences were explained to the pet owner and consent was obtained before enrolling them in the study.
 
Study design and experimental details
 
A total of 18 client-owned dogs with a history of joint inflammation, hip dysplasia and arthritis were selected (n=18) and supplemented with one tablet of Mobility Plus® until complete recovery. The dogs were used as their own controls and, therefore, allocated to a control pre-treatment period (0 days), followed by a treatment period (45 days). Efficacy of the product was judged based on the recovery from pain and inflammation (Improvement in assessment parameters scores). Based on the severity of the disease, dogs were treated with Meloxicam injection. Meloxicam injection was administered initially as a single dose at 0.2 mg/kg body weight intravenously or subcutaneously. Concurrently, any crusts due to skin injury were gently removed with a brush, cleaned with sterile saline solution and wiped with dry sterile cotton. When Mobility Plus® was administered to the dogs, concurrent treatment with another analgesic, antipyretic and anti-inflammatory supplements was not followed.
 
Evaluation of the study parameters
 
The changes in assessment parameters scores, viz. lameness score, joint mobility score, pain on palpation score and weight-bearing score and the overall clinical condition score were evaluated after supplementation with Mobility Plus® to assess its role in the management of osteoarthritis and joint disorders in dogs according to the grading system (McCarthy et al., 2007), as described in Table 1.
 

 
Statistical analysis
 
Data were expressed as mean ± standard error of the mean and subjected to two-way analysis of variance followed by Bonferroni test to draw the comparison between before treatment (day 0) and during treatment (i.e., days 15, 30 and 45). P value, p≤0.05, was considered statistically significant.

Existing medications, such as NSAIDs, for the management of inflammation are not viable given their severe adverse effects, viz. bleeding and ulceration. Colchicine and corticosteroids are related to an expanded danger of toxic signs along with severe complications, such as bone marrow demolition and deterioration of liver or kidney cells (Schlesinger. 2004). For the best possible control and alleviation of inflammatory reactions, natural products are used as therapeutic solutions to control the aggravation of osteoarthritis (Tanwar et al., 2015). Hence, this study evaluated the in vivo efficacy of Mobility Plus® in managing osteoarthritis and joint inflammation in dogs.
       
The assessment parameters scores viz. lameness, joint mobility, pain and weight-bearing scores, significantly (p<0.001) decreased in dogs as early as day 15 after supplementation with Mobility Plus® along with standard treatment; hence, the overall clinical condition score significantly (p<0.001) decreased as early as day 15 after Mobility Plus® supplementation. However, the complete amelioration of lameness, joint mobility, pain and weight-bearing was observed on day 45 (Table 2). The amelioration of lameness, joint mobility, pain and weight-bearing of dogs after supplementation could be attributed to the antiarthritic, anti-inflammatory and analgesic activities of Mobility Plus®.
 

       
The antiarthritic, anti-inflammatory and analgesic activities of Mobility Plus® could be understood by individual herbal ingredients, viz. Z. officinale, A. sativum, P. americana, G. max, A. comosus and C. wightii, present in Mobility Plus®. It has been reported that gingerol, shogaol and other structurally related substances in ginger inhibit prostaglandin and leukotriene biosynthesis by suppressing 5-lipoxygenase or prostaglandin synthetase (Hassan et al., 2017). These chemicals can also inhibit the synthesis of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor-α (TNF-α) and IL-8 (Tjendraputra et al., 2001; Verma et al., 2004). Paw oedema in carrageenan-induced rats was considerably reduced by treatment with 400 mg/kg aqueous ginger extracts compared to untreated rats (p<0.001). Hence, it was understood from the findings of Hassan et al., (2017) that the aqueous extract of Z. officinale possesses anti-inflammatory properties.
       
A. sativum extract and its related phytochemicals have been reported to possess anti-inflammatory activity. Hobauer et al., (2000) and Gu et al., (2013) observed that the anti-inflammatory activity of A. sativum extracts is caused by inhibiting the emigration of neutrophilic granulocytes into the epithelia. Jeong et al., (2016) reported that aged black garlic (ABG) exhibited potent antioxidant activities and these activities were found responsible for its anti-inflammatory activity. Furthermore, they revealed that ABG chloroform extract acts by reducing nuclear factor-êB (NF-êB) activation in human umbilical vein endothelial cells caused by TNF-α. Moreover, ABG methanolic extract was reported to prevent cyclooxygenase-2 and prostaglandin E₂ (PGE₂) production by NF-êB inactivation.
       
In a prospective multicenter randomised control trial, Blotman et al., (1997) reported that 153 osteoarthritis patients treated with avocado/soybean unsaponifiables (ASU) along with NSAIDs for 45 days reduced the requirements of NSAIDs without significant changes in patients’ pain scores. Ernst (2003) conducted three clinical trials to assess the effectiveness of ASU therapy on osteoarthritis patients and two of them demonstrated a reduction in Lequesne’s functional index, pain and disability. Furthermore, more than 50% reduction in NSAID requirement was observed in 71% of the patients in the case group compared to control (36%) (Ernst, 2003). Maheu et al., (2014) reported no improvement in joint space width (JSW) during 3 years of follow-up in the hip in osteoarthritis patients on ASU therapy. However, 20% prevention of JSW aggravation was noticed.
       
Based on the literature, A. comosus possesses several medicinal properties, viz. anti-inflammatory (Secor et al., 2005), antirheumatic (Kargutkar and Brijesh, 2016) and other immunomodulatory (Engwerda et al., 2001). Kargutkar and Brijesh, (2016) confirmed the anti-inflammatory property of A. comosus leaf extract through its inhibitory effect on carrageenan-induced paw oedema in rats. Furthermore, these authors postulated that the possible mechanism of action of the anti-inflammatory activity of A. comosus leaf extract could be through the inhibition of protein denaturation, proteinase activity and synthesis of TNF-α, IL-1β, PGE₂ and reactive oxygen species (Kargutkar and Brijesh, 2018). The fruit and stem parts of A. comosus are rich sources of bromelain. Bromelain belongs to a group of protein-digesting enzymes reported to possess antiarthritic, anti-inflammatory and analgesic properties. It has been recorded that treatment with the combination of bromelain, trypsin and rutin resulted in the reduction of pain and inflammation, which was at par when compared to diclofenac treatment (Akhtar et al., 2004). According to Brien et al., (2004) bromelain as a feed supplement could be recommended as an alternative treatment to NSAIDs. Mojcik and Shevach (1997) reported the pivotal role of bromelain in the pathogenesis of arthritis. In addition, bromelain has analgesic properties that are thought to be the result of its direct influence on pain mediators, such as bradykinin (Pavan et al., 2012; Maurer 2001).
       
Guggulsterone [4,17(20)-pregnadiene-3,16-dione] is a plant sterol derived from the gum resin (guggul) of the tree C. wightii. The resin of the C. wightii tree has been used in Ayurvedic medicine for centuries to treat diseases such as obesity, bone fractures, arthritis, inflammation, cardiovascular disease and lipid disorders (Urizar and Moore, 2003; Sinal and Gonzalez, 2002). Furthermore, literature reports evidenced the effectiveness of guggul for treating knee osteoarthritis (Khanna et al., 2007; Singh et al., 2003).
       
In summary, this study demonstrated that joint inflammation and osteoarthritis in dogs were ameliorated after supplementation with Mobility Plus® along with standard treatment through the antiarthritic and anti-inflammatory activities of the individual ingredients present in Mobility Plus®. Hence, this study provided considerable preliminary data that Mobility Plus® has antiarthritic and anti-inflammatory activities.

It was demonstrated that Mobility Plus® would play a major role in the management of osteoarthritis-induced inflammation through the antiarthritic and anti-inflammatory activities of individual ingredients present in Mobility Plus®. Hence, Mobility Plus® could be recommended for the amelioration of joint inflammation and osteoarthritis conditions in canines.

We thank Dr. Rajesh Kumawat and Dr. U.V. Babu for their kind encouragement.