Indian Journal of Pain

: 2018  |  Volume : 32  |  Issue : 1  |  Page : 16--23

Aflapin®: A novel and selective 5-lipoxygenase inhibitor for arthritis management

Manoj A Suva1, Dharmesh B Kheni1, Varun P Sureja2,  
1 Scientific and Medical Affairs, Sundyota Numandis Group of Companies, Ahmedabad, Gujarat 380015, India
2 Medical and Business Affairs, Sundyota Numandis Group of Companies, Ahmedabad, Gujarat 380015, India

Correspondence Address:
Mr. Manoj A Suva
Scientific and Medical Affairs, Sundyota Numandis Group of Companies, Ahmedabad, Gujarat 380015


Osteoarthritis (OA) is the most common form of arthritis characterized by progressive destruction of joint cartilage tissue, pain and inflammation, stiffness, and impaired physical activity. It is the most prevalent and leading cause of pain and disability across the globe. During the pain and inflammatory process, 5-lipoxygenase (5-LOX) pathway is also involved, which generates leukotrienes (LTs), namely LTB4 and cysteinyl LTs. Osteoblasts also synthesize LTs, which stimulate and enhance the production of interleukin 1, tumor necrosis factor α, and various other cytokines that are potent inflammatory mediators. LT formation leads to cartilage degradation and compensates chondrocyte-mediated cartilage repair mechanism. Current therapies include nonsteroidal anti-inflammatory drugs, analgesics, and disease-modifying agents, but do not affect 5-LOX pathway. Boswellia serrata extract–derived boswellic acids are specific, non-redox inhibitors of 5-LOX, and 3-O-acetyl-11-keto-β-boswellic acid (AKBA) possesses the most potent 5-LOX inhibitory activity. B. serrata extracts have shown significant efficacy and safety in the treatment of various inflammatory disorders such as OA, rheumatoid arthritis, asthma, and inflammatory bowel diseases. Aflapin® is a novel synergistic composition containing B. serrata extract selectively enriched with 20% AKBA and B. serrata nonvolatile oil. Aflapin® is a patented, selective, and most potent 5-LOX inhibitor, which significantly reduces joint pain, inflammation, stiffness, and improves physical function compared to placebo and other B. serrata extract. Aflapin® also significantly reduces matrix metalloproteinase levels, enhances chondrocytes proliferation, and increases glycosaminoglycans levels, thereby providing cartilage protection in arthritis. Numerous in vitro studies, preclinical studies, and clinical studies suggest the potential of Aflapin® as a useful therapeutic intervention for the management of arthritis.

How to cite this article:
Suva MA, Kheni DB, Sureja VP. Aflapin®: A novel and selective 5-lipoxygenase inhibitor for arthritis management.Indian J Pain 2018;32:16-23

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Suva MA, Kheni DB, Sureja VP. Aflapin®: A novel and selective 5-lipoxygenase inhibitor for arthritis management. Indian J Pain [serial online] 2018 [cited 2023 Feb 6 ];32:16-23
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Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions.[1] Symptoms of OA include joint pain, joint inflammation and stiffness, and muscle weakness, which can range from mild to severe. Local risk factors for OA include obesity, occupation, injury, and physical activity/sports, whereas systemic risk factors include age, gender, genetics, hormones, and diet.[2]

 Osteoarthritis Pathophysiology

OA is a complex and chronic disorder. Exact pathophysiology of OA is not understood completely till date; however, its initiation, progression, and severity may be influenced by multiple factors. Two key features involved in OA include (i) joint inflammation and pain and (ii) cartilage degradation. Joint inflammation and pain are the most common complaining features of most of the patients with OA and reason to consult a doctor. Cyclooxygenase (COX) pathway responsible for inflammation is very well known, but that is not the only pathway contributing to inflammation and pain in OA. There are varieties of mediators other than COX having a role in the overall painful inflammatory process.[3] Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) act by COX inhibition. Although 5-lipoxygenase (5-LOX) was discovered many years ago, the drug inhibiting 5-LOX was not discovered; hence, the pathway remained unaddressed. Emerging evidences suggest that 5-LOX pathway is involved not only in the joint inflammation but also in the cartilage degradation leading to arthritis progression.

 5-Lipoxygenase and Leukotrienes: Newer Targets in Arthritis Pathophysiology

It is now well understood that many of the prostaglandin-affected pathophysiologic processes in OA are also affected by other mediators, specifically leukotrienes (LTs). Arachidonic acid is also a substrate for 5-LOX. The 5-LOX pathway is involved in the generation of LTs, namely LTB4 and cysteinyl LTs such as LTA4, LTB4, LTC4, LTD4, and LTE4. LTs thus formed are potent mediators of inflammation, causing increased activation, recruitment, migration, and adhesion of immune cells. Osteoblasts also synthesize LTs. In fact, higher levels of LTB4 and prostaglandins have been reported in the joints of the patients with OA compared to those of healthy individuals. In osteoblasts, LTB4 is reported to stimulate and enhance the production of interleukin (IL)-1 and tumor necrosis factor (TNF)-α. They might mediate the cartilage damage by promoting the expression of the degrading enzymes or by compensating the chondrocyte-mediated mechanisms for the repair of damaged cartilage.[4] LTB4 is a potent chemotactic and chemokinetic mediator and acts as a leukocyte activator by stimulating migration and activation of granulocytes and T cells, leading to adherence of granulocytes to vessel walls, degranulation and release of the cathelicidin LL-37 and superoxide, enhancement of phagocytic activity of neutrophils and macrophages, and stimulation of immunoglobulin secretion by lymphocytes. These properties imply a significant role for LTB4 in the regulation of the immune response and in the pathogenesis of inflammatory diseases such as arthritis.[5] These properties of LTB4, similar to prostaglandin E2, might also be responsible for its ability to stimulate the bone resorption in OA. The probable role of 5-LOX pathway in OA pathophysiology is shown in [Figure 1].[3],[6],[7],[8],[9],[10] Laufer [11] concluded that OA subchondral osteoblasts can synthesize LTB4, indicating a role of LTs in bone remodeling associated with OA. Sahap Atik [12] mentioned that LTB4 activity was found to be significantly higher in patients with OA suggesting the pathogenic role of LTs in OA. Most commonly used therapies in the management of OA include NSAIDs, analgesics, and disease-modifying osteoarthritic drugs. Though all of these are effective intervention in the management of OA, they do not act on 5-LOX pathway. NSAID intake is associated with high prevalence of gastrointestinal, cardiovascular, and renal adverse effects. All efforts to develop NSAIDs that spare the gastrointestinal tract and the cardiovascular system are still far from achieving a breakthrough.[13],[14] Moreover, NSAIDs can cause a disruption of glycosaminoglycan (GAG) synthesis, accelerating the articular damage in arthritic conditions.[15],[16],[17],[18] 5-LOX and LTs are involved in pain, inflammation, and cartilage-degrading process of OA. Hence, a therapeutic intervention targeting 5-LOX can be an attractive approach to manage the progression of OA. As a consequence, the interest in alternative, well-tolerated, anti-inflammatory natural remedies has reemerged in the current era.{Figure 1}

 Introduction to Boswellia serrata

Boswellia serrata is a type of deciduous tree, which grows naturally in the Indian subcontinent. B. serrata and other Boswellia species are also called as frankincense or olibanum.[19] The use of oleo gum resin of B. serrata (salai guggal) is described in Ayurvedic textbooks (Charaka Samhita, first to second century AD, and in Ashtanga Hridaya Samhita, seventh century AD). For centuries, B. serrata gum resin has been used in the treatment of various inflammatory diseases, including arthritis, respiratory tract diseases, and chronic colitis, and also it has numerous pharmacological activities, namely antiulcer, hepatoprotective, wound healing, antioxidant, antimicrobial, and analgesic.[19],[20],[21],[22],[23],[24],[25],[26],[27] The pentacyclic triterpenic acids, named boswellic acids (BAs), present in the gum resin of B. serrata are the main constituents responsible for its anti-inflammatory property.[28] Suppression of LT synthesis by inhibiting 5-LOX is considered the main mechanism underlying their anti-inflammatory effect.[29] BAs are specific and non-redox inhibitors of 5-LOX, and they do not affect 12-LOX and COX activities.[21],[28],[30],[31] The pentacyclic triterpene ring is crucial for binding to the enzyme, whereas functional groups (11-keto function in addition to a hydrophilic group on C4 of ring A) are essential for the 5-LOX activity.[32] Among the known BAs, 3-O-acetyl-11-keto-β-boswellic acid (AKBA) possesses the most potent inhibitory activity on 5-LOX.[21],[33],[34]B. serrata gum resin extract showed concentration-dependent inhibition of LTB4 and 5-hydroxyeicosatetraenoic acid synthesis in vitro.[35]B. serrata–derived BAs were shown to have antiulcer effect against different experimental models.[13]B. serrata extracts, besides their reported capacity in dampening the inflammatory response together with counteracting the oxidative stress, were also able to influence the regulatory and effector T cell compartments as observed in an ex vivo study.[36] A significant number of studies support that Boswellia extract is beneficial for patients with various diseases such as bronchial asthma, Crohn's disease, OA, and rheumatoid arthritis.[27],[37],[38]

 Development of AKBA-Enriched B. serrata Extract

AKBA is the most active constituent of frankincense. It is present in very less amount, which is approximately 2%–3% in higher grade B. serrata extracts. Laila Nutraceuticals Research and Development Center, India, had developed a standardized novel Boswellia compound comprising 30% AKBA (known as BE-30 or 5-Loxin) to generate more efficacious anti-inflammatory product. Its efficacy was established at molecular, genetic, and cellular levels using enzymatic and cell-based assays, and its beneficial effects were confirmed by in vivo studies. Its safety was proven through preclinical safety studies and its non-genotoxic nature was established using bacterial reverse mutation test (Ames test), mouse lymphoma test, and chromosomal aberration assays.[39] In human genome screen study, BE-30 was shown to downregulate several important genes related to inflammation, cell adhesion, and proteolysis in TNF-α-induced human microvascular endothelial cells (HMECs).[40],[41] BE-30 was also shown to almost completely abrogate the gene expression and activities of matrix metalloproteinase (MMP)-3, -10, and -12 in TNF-α-induced HMECs.[42] BE-30 exhibited significantly better anti-inflammatory efficacy than the regular Boswellia extract containing 3% AKBA in Freund's adjuvant–induced arthritis model of rats.[41],[42] Molecular-level studies showed that BE-30 inhibited the production of proinflammatory cytokine TNF-α and it downregulated the key modulatory proteins of 5-LOX–arachidonic acid cascade such as 5-LOX-activating protein and 5-LOX in lipopolysaccharide (LPS)-induced THP-1 human monocytic leukemia cell line. BE-30 downregulated mitogen-activated protein kinase/nuclear factor κB (NFκB) activation in LPS-induced human monocytes, which are the key players responsible for a variety of cellular responses including inflammation.[39],[43] AKBA turned out to be a natural inhibitor of NF-κB and oxygen radical formation in polymorphonuclear neutrophils.[44],[45] Anti-inflammatory properties of B. serrata extracts were investigated in human peripheral blood mononuclear cells (PBMCs) and mouse macrophages, where methanolic extract of B. serrata downregulated TNF-α, IL-1β, and IL-6 mRNA expression and inhibited the production of nitric oxide (NO).[46] In addition, BAs inhibited leukocyte elastase, cytokines (ILs and TNF-α), and the complement system, which may also contribute to the anti-inflammatory properties of Boswellia extract.[46],[47] Inhibition of TNF-α and its signaling has been recognized as a highly successful strategy for the treatment of chronic inflammatory diseases such as rheumatoid arthritis.[44] Collectively, these findings provide molecular basis for the anti-inflammatory properties of B. serrata extract containing AKBA.[39] A broad-spectrum safety of BE-30 was established in acute oral, acute dermal, primary skin, and eye irritation, and a 90-day subchronic toxicity study was conducted in various animal models.[48] Furthermore, a double-blind placebo controlled human clinical study suggests that BE-30 is significantly effective in improving various pain scores in patients with OA. Interestingly, the improvement in pain scores in the treated subjects is correlated with the reduction of synovial fluid MMP-3, a potent cartilage-degrading enzyme.[49] These evidences suggest the efficacy and safety of highly standardized AKBA containing B. serrata extract. However, a series of pharmacokinetic studies conducted in humans and in animal models indicate that after oral administration of Boswellia products, sufficient systemic concentration of AKBA is required for its anti-inflammatory activities.[50],[51],[52],[53],[54] Poor absorption through intestine and/or extensive metabolism is the crucial factor affecting the systemic availability of AKBA and thus limiting the anti-inflammatory efficacy of Boswellia products.[54] Therefore, attempts were made to achieve an increased systemic availability of AKBA to improve further the anti-inflammatory potential of B. serrata extracts.

 Aflapin®: Most Potent and Selective 5-Lipoxygenase Inhibitor

Aflapin® is a patented and most potent selective 5-LOX enzyme inhibitor developed by Laila Nutraceuticals Research and Development Center, India. Aflapin® is a novel synergistic composition containing B. serrata extract selectively enriched with AKBA and B. serrata nonvolatile oil.[55] It offers pleiotropic benefits acting on multiple cellular events of OA.[56] It possesses superior efficacy as an anti-inflammatory, cartilage-protective, anti-osteoarthritic agent, and exhibits better bioavailability compared to BE-30 and other B. serrata extracts commercially available in the market.[56],[57] The chemical structure of the pentacyclic triterpene AKBA [58] and mechanism of action of Aflapin ®[55] are shown in [Figure 2] and [Figure 3], respectively.{Figure 2}{Figure 3}

 Pharmacological Action of Aflapin®

5-LOX inhibition: In an in vitro study, Aflapin® (100 mg/kg) showed 21.06% more inhibition of 5-LOX activity compared to BE-30 (100 mg/kg).[56]Anti-inflammatory action: Anti-inflammatory action of Aflapin® was compared with that of BE-30 in preclinical study by various parameters as follows:

Paw edema volume reduction: Anti-inflammatory effect of Aflapin® (100 mg/kg) was measured in Freund's Complete Adjuvant (FCA)-induced animal model of inflammation. Other treatment groups in the same experiment included BE-30 (100 mg/kg), prednisolone (10 mg/kg), and control group. Aflapin® and BE-30 provided 53.6% and 36.7% protection, respectively, measured as reduction in paw edema volume from FCA-induced inflammation in the rat model. In addition, the protection provided by Aflapin® is significantly better than that by BE-30 in FCA-induced inflammation.[56],[59]TNF-α: TNF-α cytokine is one of the major inflammatory cytokines responsible for the joint inflammation. Previously it has been shown by Syrovets et al.[60] that acetyl-α-BA and AKBA inhibited the generation of TNF-α in lipopolysaccharide-stimulated human monocytes, whereas AKBA was found to be the most active compound. Aflapin® and BE-30 significantly reduced TNF-α level by 65.04% and 38.83%, respectively, compared to vehicle control group.[41]Intercellular Adhesion Molecule-1 (ICAM-1): Adhesion molecule expression on endothelial cells helps in the diapedesis of inflammatory cells in the synovial fluid. In vitro studies showed that Aflapin® significantly reduces TNF-α-induced ICAM-1 expression. Aflapin® shows more capability to reduce ICAM-1 secretion than that of BE-30.[61]

Cartilage protection: Collagen is an important component of the cartilage ECM, providing tensile strength to the tissue. In arthritis, collagen degradation is initiated by collagenases such as MMPs. MMP is a family of enzymes responsible for the degradation of ECM. Higher activity of MMPs is responsible for cartilage degradation. MMPs are expressed and synthesized by different cell types present in the joint, including synovial cells and chondrocytes, in response to proinflammatory cytokines such as IL-1. Aflapin® and BE-30 significantly inhibited MMP-3 production in TNF-α-induced human synovial cells. Aflapin® provided 14.83% better efficacy in inhibiting MMP-3 production compared to BE-30.[36],[56]Chondroprotective action: Chondrocyte destruction is a key pathophysiological feature of osteoarthritic joint. Under the influence of various proinflammatory cytokines such as IL-1β and TNF-α, chondrocytes can be destroyed. An in vitro study suggested the protective effect of Aflapin® against the chondrocyte-destructive property of IL-1β proinflammatory cytokine by assessing cellular proliferation index, which was also compared with BE-30 in dose-dependent manner. The presence of increased numbers of apoptotic cells or the reduction in viable chondrocytes correlates with the extent of cartilage matrix loss under inflammatory conditions in OA. Dying cells exhibit significant decrease in MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) reductive activity, which helps to measure the extent of cell death. In MTT-based cell proliferation assay, Aflapin® and BE-30 showed significant improvements in cell proliferation in IL-1β-treated human chondrocytes in dose-dependent manner. Results showed that Aflapin® provides significantly better protection from loss of cellular viability than BE-30. Aflapin® modulates the cell proliferation of human primary chondrocytes treated with a proinflammatory cytokine, IL-1β.[56],[61],[62]Anabolic effect on cartilage tissues: Early stage of destructive joint diseases such as OA and rheumatoid arthritis is characterized by reduced synthesis of matrix proteoglycans in chondrocytes and subsequent loss of matrix substances from articular cartilage. GAGs are the nonprotein part of proteoglycans. Proinflammatory cytokine, IL-1β, specifically reduces proteoglycan synthesis in articular cartilage. An in vitro study using human primary chondrocytes treated with IL-1β showed significant reduction in GAG content by 23.08%. Treatment with Aflapin® and BE-30 significantly increased GAG content in dose-dependent manner. Aflapin® provided significantly better recovery of GAG content in chondrocytes than BE-30.[56]Bioavailability study of Aflapin®: AKBA present in B. serrata has poor bioavailability due to its lipophilic nature. Hence, a comparative assessment of bioavailability of AKBA in serum was conducted with 100 mg/kg of Aflapin® and BE-30 as a single-dose administration into Sprague Dawley (SD) rats. Results showed that Aflapin® was 51.78% more bioavailable than BE-30. The area under curve of Aflapin® was greater compared to that of BE-30 (14.07 of Aflapin® vs. 9.27 of BE-30). In addition, Aflapin® provided longer retention of peak concentration of AKBA in systemic circulation than BE-30, as shown in [Figure 4].[56] Aflapin® has a superior bioavailability than BE-30 due to the presence of nonvolatile oil fraction. Hence, it suggests that the nonvolatile oil fraction present in Aflapin® might be acting as a vehicle, which provides the basis for more bioavailable AKBA in the systemic circulation and to reach to the target cells.[56]{Figure 4}

 Aflapin® Clinical Trials Summary

A double-blind, randomized, placebo controlled study was conducted in 75 subjects with medial tibiofemoral OA symptoms to validate the efficacy of different dosages of BE-30 (30% AKBA) (clinical trial registration number: ISRCTN05212803). In all groups consisting of 25 patients, each received 100 mg of BE-30 (30% AKBA), or 250 mg of BE-30 (30% AKBA), or placebo orally once daily for 90 days. Pain, stiffness, and physical functions were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale of 0 to 100 units; pain was assessed by visual analog scale (VAS); and physical function was assessed by Lequesne Functional Index (LFI) at day 0, 7, 30, 60, and 90, respectively. Both doses of BE-30 conferred clinically significant improvements in pain scores and physical function scores in patients with OA. BE-30 (30% AKBA) in 250-mg dose showed improvements in pain score and functional ability in 7 days after the start of treatment.[49] Aflapin® is a novel synergistic composition containing B. serrata extract selectively enriched with 20% AKBA and B. serrata–specific nonvolatile oil. A double-blind, randomized, placebo controlled study was conducted in subjects with mild-to-moderate OA symptoms to validate the efficacy of Aflapin® in the management of clinical symptoms of OA of the knee (Alluri Sitarama Raju Academy of Medical Sciences [ASRAM], Eluru, Andhra Pradesh, India; clinical trial registration number: ISRCTN69643551). A total of 60 subjects between the age of 40 and 80 years having unilateral or bilateral OA of the knee according to the criteria of the American College of Rheumatology for more than 3 months were recruited. The subjects were randomly assigned to receive either Aflapin® 50 mg orally twice daily in encapsulated form or placebo for 30 days. Pain, stiffness, and physical functions were assessed by WOMAC scale (0 to 100 units); pain was assessed by VAS score; and physical function was assessed by LFI scale at day 0, 5, 15, and 30. Results showed that Aflapin® conferred clinically significant improvements in WOMAC pain score by 49.37%, stiffness score by 48.45%, and physical function score by 45.26%; VAS score by 48.96%; and LFI score by 34.38% in patients with OA. Interestingly, Aflapin® was shown to improve joint pain in as early as 5 days from the start of treatment. Several serum, urine, and whole blood parameter assessment during clinical trials showed no significant change from baseline. These results suggest that Aflapin® is a safe, fast-acting, and effective therapeutic intervention in the management of OA.[55] Another clinical trial was performed to assess the comparative efficacy and tolerability of Aflapin® (20% AKBA and B. serrata–specific nonvolatile oil) and BE-30 (30% AKBA) in the treatment of OA of knee (ASRAM; clinical trial registration number: ISRCTN80793440). In the study, 60 subjects with OA received 100 mg BE-30 (n = 20), or 100 mg Aflapin® (n = 20), or placebo (n = 20) orally daily for 90 days. The subjects were assessed for pain and physical functions by using standard tools WOMAC score, VAS score, and LFI scale at day 0, 7, 30, 60, and 90. Results showed that both BE-30 and Aflapin® produced clinically significant improvements in pain scores and physical function scores. Results showed that Aflapin® conferred clinically significant improvements in WOMAC pain score by 69.11%, stiffness score by 70.13%, and physical function score by 61.43%; improvement in VAS score by 57.65%; and improvement in LFI score by 41.67% in patients with OA. Aflapin® group that received Aflapin® 100 mg orally daily showed significant improvement in pain score and functional ability as early as 7 days of treatment. Aflapin® showed better efficacy compared to BE-30 in all clinical parameters.[61] Aflapin® acts on cellular and molecular mechanisms associated with the pathologic processes of chronic arthritis diseases, and hence possesses significant therapeutic efficacy with fast onset of action.[63]

 Safety of Aflapin®

Safety evaluation of Aflapin® was carried out by acute and subacute toxicity studies conducted in various animal models according to the Organisation for Economic Co-operation and Development (OECD) test guidelines. Aflapin® was administered to female SD rats by oral gavage using a graduated syringe and intubation cannula. The acute oral lethal dose (LD50) of Aflapin® (single administration) was found to be greater than 5000 mg/kg body weight in female SD rats following an observation period of 14 days. Acute dermal LD50 of Aflapin® (topical administration, once daily) was greater than 2000 mg/kg in SD rats during the period of 14 days. Aflapin® was moistened with distilled water and a dry paste was prepared having 75% w/w mixture concentration, which was applied once topically to pad and entire trunk of New Zealand white rabbits for primary dermal irritation study, and the results showed absence of irritation to skin. A primary eye irritation test was conducted in New Zealand albino rabbits to determine the potential for Aflapin® to cause irritation from a single instillation via the ocular route. No corneal opacity or iritis was observed in any of the treated eyes after Aflapin® administration. A repeat dose in a 28-day subacute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The no observed adverse effect level (NOAEL) of Aflapin® was found to be greater than 2500 mg/kg body weight, and it demonstrated broad-spectrum safety in animal models. In randomized, double-blind placebo controlled clinical trials, several biochemical, hematological, and urine parameters were analyzed for the safety assessment as given in [Table 1]. Aflapin® did not cause any significant changes in biochemical (serum and urine) and hematological parameters compared to placebo from baseline, indicating that it is relatively a safer therapy. During the 30- and 90-day clinical study, Aflapin® did not produce any major adverse events.[55],[61] Hence, Aflapin® 100 mg per day oral dosage is safe and well tolerated for patients with arthritis. In addition, B. serrata has a long history of different traditional uses with numerous modern clinical applications. In a clinical trial, B. serrata up to 6 g/day as oral dosage administered for 2 months to patients with OA showed significant effect in improving overall arthritis symptoms, and no side effects were reported.[64]B. serrata gum resin is included in the list of substances Generally Recognized As Safe by the US Food and Drug Administration.[65] On the basis of the observations made in the frame of the aforementioned clinical trials, adverse effects of B. serrata extract were consistently rare and were judged as not related to the treatment and not markedly different from those noted in the placebo group. Hence, oral preparations of B. serrata extract formulations are safe to use within clinically validated doses.{Table 1}


OA is a multifactorial disease characterized by progressive destruction of joint cartilage tissue, pain and inflammation, stiffness, and impaired physical activity. 5-LOX pathway mediated synthesis of LTs and various inflammatory cytokines, which led to pain, inflammation, and cartilage degradation during arthritis. Most of the NSAIDs act by inhibiting COX enzyme; however, the 5-LOX enzymatic pathway remains unaddressed. Aflapin® is a selective and potent 5-LOX inhibitor, which significantly reduces the synthesis of LTs and various inflammatory mediators, and thereby reduces joint pain, inflammation, and stiffness, and improves physical function. Aflapin® is also shown to inhibit MMPs, and thereby prevents cartilage degradation and controls arthritis disease progression. Due to the synergy of AKBA and nonvolatile oil in Aflapin®, it shows greater and faster action in reducing pain and inflammation than other B. serrata extracts owing to its higher bioavailability. These evidences suggest the potential promise in favor of Aflapin® as a useful therapeutic strategy for arthritis management.

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Conflicts of interest

All authors have declared that the present information provided is extensively reviewed from scientific databases such as PubMed, ScienceDirect, and Google Scholar sources, and they have included relevant information on the subject. The authors are employees of Sundyota Numandis Group of Companies.


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