According to population-based studies, the global prevalence of RA between 1980 and 2019 was 460 per 100,000 population. Trend analysis showed that RA was observed more in developed countries than developing countries (Almutairi, 2020, pp. 863-877). Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the symptomatic treatment options for RA. However, these medications are known to have multiple adverse effects including nephrotoxicity, gastrointestinal bleeding and ulceration, increasing blood pressure and the risk of first hospitalization due to congestive heart failure. Conventional disease modifying anti-rheumatic drugs (DMARDs) are usually the first choice to diminish disability and improve long-term outcomes for people with RA. Biologics are much more costly than other subsets of DMARDs, they are commonly used as partial responders to traditional DMARDs. Although the combination of biologics and traditional DMARDs has demonstrated improved efficacy, the potential benefits and harms (such as cancer and infections) are still controversial. However, in spite of applying aggressive pharmacologic treatment regimens early in disease onset, complete clinical remission is not achieved (Guo et al., 2018, p.15). Although biological medications seem to effectively target molecular pathways involved in the inflammatory process of RA, there is a lack of long-term safety data regarding their use. Various investigations have demonstrated an increased prevalence in the use of herbal medicine in developing countries. Interestingly, a rise in the prevalence of herbs used as complementary and alternative medicine among chronic disease patients has been reported in recent years. The anti-inflammatory properties of some herbal products are well-known and they have fewer unwanted effects than existing anti-inflammatory medications. As such, herbs and their derivatives constitute a promising arena in novel medical therapies. Furthermore, the cost-effectiveness of natural products has been explored and summarized by high quality studies. Certain phytochemicals are considered to inhibit the release of inflammatory molecules to suppress inflammatory responses (Gandhi et al., 2022, pp.1-15). is the precursor of ellagitannin and has been reported to be the most active polyphenol obtained from different parts of the pomegranate tree (Punica granatum Linn.). Methanolic (and ethanolic) pomegranate peels extract contains a high amount of bioactive compounds including punicalagin (10-50 mg∕g) ( Xu et al., 2021, pp.1-12). Historically, seeds and juices are believed to have been taken as supplements to reduce the clinical symptoms of RA (Singh, Singh, & Mahajan, 2020, pp. 1306-1327). Marques and coauthors (2016) have already revealed that Punicalagin diminished TNF α and interleukin (IL) 6 secretion in macrophages and primary human chondrocytes with lipopolysaccharide (LPS)-induced inflamed RAW264.7. (Marques et al., 2016, pp- 463-1467). Anthocyanins have been shown to represent potent anti-inflammatory, anti-oxidant, anti-cancer, anti-obesity and immunomodulatory activity. (Salehi et al., 2020, pp.1-20). Min and coauthors (2015) reported inhibitory effect of ACNs on osteoclasts via the downregulation of cytokines including IL-1, IL-6, IL-17, and TNF-α in vitro. the study showed EA reduced cartilage destruction, synovial hyperplasia and bone erosion generated by Freund’s adjuvant. Significant suppression of caspase-3 expression in models treated with EA testifies to the anti-apoptotic property of this biologic compound (Fikry, Gad, & Eid, 2019, pp. 878–886).
According to the international agency for research on cancer 1 in 5 people develop cancer during their lifetime, suggesting that more than 50 million people are living within five years of a past cancer diagnosis (World Health Organization (WHO, 2020, para. 1). Despite novel approaches like nanomedicine, targeted therapy, and immunotherapy in cancer treatments during the last decades, chemoresistance has remained the chief hurdle in eliminating cancerous cells (Elgendy , Alyammahi & Alhamad, 2020, p. 103095). About 9 out of 10 cancer deaths are due to spreading of cancer cells from the primary tumor mass towards close and far tissues (a process called metastasis). Treatment failure followed by consequent recurrence of cancer cells and metastasis is the leading cause of death. Many survivors suffer from serious acute or chronic complications after cancer therapy (Qian, Mei, & Zhang, 2017, p.38). Furthermore, chemotherapy commonly induces a variety of side-effects in patients as a result of nonspecific action against both normal cells and cancerous cells. For instance, chemotherapeutic drugs result in alopecia by affecting not only fast dividing cancer cells, but hair follicles as well. Nausea and vomiting are the most common symptoms induced by chemotherapy, with gastrointestinal symptoms including diarrhea (and in some cases constipation) being another common side effect. Chemotherapy is also known to impair immune function and bone marrow activity (Li et al., 2020, p.599073). The identification of approved doses of anticancer drugs is another point to be given careful attention, especially those with higher cost and administered for a longer duration. Larger doses of chemotherapeutic drugs may increase the risk and severity of the aforementioned side effects, and are not cost-saving. Therefore, phytomedicines should be considered as an option not only for adjuvant therapy, but also in view of their comparatively low toxicity and ability to diminish adverse effects of chemotherapy in cancer patients. Natural products and their derivatives can be used as novel therapeutic interventions with improved pharmacological properties targeting tumor cells (Meriggi & Zaniboni, 2020, pp.1–11).
Use of monoclonal antibodies (mAbs) in feild of diagnostic and therapy is evident. They are developed to treat cancer, immune and infectious diseases (Rajewsky, 2019). Biologic agents are essential alternative for treating different skin diseases. Etanercept, infliximab and adalimumab are used to treat moderate-tosevere plaque psoriasis. These mAbs inhibit TNF (Tumor necrosis factor)-α and approved by FDA (US Food and Drug Administration). Also, Secukinumab and ixekizumab are anti IL-23/IL-17A receptors that received FDA approval and show high efficacy to treat plaque psoriasis. It is worthy of note that secukinumab received FDA approval for arthritic psoriasis. The biosimilars for the 3 anti-TNF-a etanercept, adalimumab and infliximab have been officially FDA approved since 2016 and represent a potential cost savings (Veilleux; Shear, 2017). Dupilumab is a IL-4 receptor-α antibody that inhibits IL-4 and IL-13 signaling targeting atopic dermatitis (AD). This agent showed valid results in phase 3 trial and still under investigation by Eroupian union and Japan according to safety and efficacy. There are some other biologic agents as like Mepolizumab, Tralokinumab, lebrikizumab, Nemolizumab, Ustekinumab and Apremilast in a phase II study in the therapy of AD. (Veilleux; Shear, 2017, Del Rosso (2019). Dacarbazine and IL-2 are two new FDA approved medications for advanced melanoma, although survival rate was not improved by these drugs. Ipilimumab is a fully human mAb (IgG1) that restricts T cell activation by inhibiting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4); drug showed these effects in phase 3 trial and enhanced survival in melanoma. Dabrafenib and and trametinib are inhibitors of the mitogen-activated protein kinase pathway and FDA approved in melanoma. For some of these drugs response rate is high although, duration of maintenance of effect is low. Ipilimumab represent only 10.9% response rate is but with a quite high maintained response of 60% at 2 years. Pembrolizumab and nivolumab, programmed cell death-1 (PD-1) inhibitor antibodies with 30% to 40% and durable response rate. Demonstrating some adverse effects in patients giving immunotyherapy should be considered. Using lower doses with assuring response rate may minimize side effects. Pidilizumab and atezolizumab are some other PD-1 targeting agents under different phases of investigations. Biologic agents may be possible effective approaches for patients with hidradenitis suppurativa (HS).
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