Current Treatments, Emerging Therapeutics, and Natural Remedies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, lifelong disorder characterized by inflammation of the gastrointestinal (GI) tract. The exact etiology of IBD remains incompletely understood due to its multifaceted nature, which includes genetic predisposition, environmental factors, and host immune response dysfunction. Currently, there is no cure for IBD. This review discusses the available treatment options and the challenges they present. Importantly, we examine emerging therapeutics, such as biologics and immunomodulators, that offer targeted treatment strategies for IBD. While many IBD patients do not respond adequately to most biologics, recent clinical trials combining biologics with small-molecule drugs (SMDs) have provided new insights into improving the IBD treatment landscape. Furthermore, numerous novel and specific therapeutic targets have been identified. The high cost of IBD drugs poses a significant barrier to treatment, but this challenge may be alleviated with the development of more affordable biosimilars. Additionally, emerging point-of-care protein biomarkers from serum and plasma are showing potential for enhancing the precision of IBD diagnosis and prognosis. Several natural products (NPs), including crude extracts, small molecules, and peptides, have demonstrated promising anti-inflammatory activity in high-throughput screening (HTS) systems and advanced artificial intelligence (AI)-assisted platforms, such as molecular docking and ADMET prediction. These platforms are advancing the search for alternative IBD therapies derived from natural sources, potentially leading to more affordable and safer treatment options with fewer side effects.

Indigenous Uses, Phytochemical Analysis, and Anti-Inflammatory Properties of Australian Tropical Medicinal Plants.

Australian tropical plants have been a rich source of food (bush food) and medicine to the first Australians (Aboriginal people), who are believed to have lived for more than 50,000 years. Plants such as spreading sneezeweed (Centipeda minima), goat's foot (Ipomoea pes-caprae), and hop bush (Dodonaea viscosa and D. polyandra) are a few popular Aboriginal medicinal plants. Thus far, more than 900 medicinal plants have been recorded in the tropical region alone, and many of them are associated with diverse ethnomedicinal uses that belong to the traditional owners of Aboriginal people. In our effort to find anti-inflammatory lead compounds in collaboration with Aboriginal communities from their medicinal plants, we reviewed 78 medicinal plants used against various inflammation and inflammatory-related conditions by Aboriginal people. Out of those 78 species, we have included only 45 species whose crude extracts or isolated pure compounds showed anti-inflammatory properties. Upon investigating compounds isolated from 40 species (for five species, only crude extracts were studied), 83 compounds were associated with various anti-inflammatory properties. Alphitolic acid, Betulinic acid, Malabaric acid, and Hispidulin reduced proinflammatory cytokines and cyclooxygenase enzymes (COX-1 and 2) with IC50 values ranging from 11.5 to 46.9 uM. Other promising anti-inflammatory compounds are Brevilin A (from Centipeda minima), Eupalestin, and 5'-methoxy nobiletin (from Ageratum conyzoides), Calophyllolide (from Calophyllum inophyllum), and Brusatol (from Brucea javanica). D. polyandra is one example of an Aboriginal medicinal plant from which a novel anti-inflammatory benzoyl ester clerodane diterpenoid compound was obtained (compound name not disclosed), and it is in the development of topical medicines for inflammatory skin diseases. Medicinal plants in the tropics and those associated with indigenous knowledge of Aboriginal people could be a potential alternative source of novel anti-inflammatory therapeutics.

Pharmaceutical Potential of Remedial Plants and Helminths for Treating Inflammatory Bowel Disease.

Research is increasingly revealing that inflammation significantly contributes to various diseases, particularly inflammatory bowel disease (IBD). IBD is a major medical challenge due to its chronic nature, affecting at least one in a thousand individuals in many Western countries, with rising incidence in developing nations. Historically, indigenous people have used natural products to treat ailments, including IBD. Ethnobotanically guided studies have shown that plant-derived extracts and compounds effectively modulate immune responses and reduce inflammation. Similarly, helminths and their products offer unique mechanisms to modulate host immunity and alleviate inflammatory responses. This review explored the pharmaceutical potential of Aboriginal remedial plants and helminths for treating IBD, emphasizing recent advances in discovering anti-inflammatory small-molecule drug leads. The literature from Scopus, MEDLINE Ovid, PubMed, Google Scholar, and Web of Science was retrieved using keywords such as natural product, small molecule, cytokines, remedial plants, and helminths. This review identified 55 important Aboriginal medicinal plants and 9 helminth species that have been studied for their anti-inflammatory properties using animal models and in vitro cell assays. For example, curcumin, berberine, and triptolide, which have been isolated from plants; and the excretory-secretory products and their protein, which have been collected from helminths, have demonstrated anti-inflammatory activity with lower toxicity and fewer side effects. High-throughput screening, molecular docking, artificial intelligence, and machine learning have been engaged in compound identification, while clustered regularly interspaced short palindromic repeats (CRISPR) gene editing and RNA sequencing have been employed to understand molecular interactions and regulations. While there is potential for pharmaceutical application of Aboriginal medicinal plants and gastrointestinal parasites in treating IBD, there is an urgent need to qualify these plant and helminth therapies through reproducible clinical and mechanistic studies.

Development of quality control parameters for two Bhutanese medicinal plants (Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B.Clarke) using traditional and modern pharmacognostical platforms.

Bhutan's scholarly traditional medical system is called Bhutanese Sowa Rigpa medicine (BSM). It was integrated with the modern healthcare system in 1967. Over 200 medicinal plants are used to produce more than 100 poly-ingredient medicinal formulations. Although BSM is supported by well-documented principles, pharmacopoeias, diagnostic procedures, treatment regimens, and traditional quality assurance systems, modern quality control parameters have become essential to distinguish closely related species and prevent contamination from exogenous impurities. This study aims to establish reliable analytical methods and quality control parameters for Aster flaccidus Bunge and Aster diplostephioides (DC.) Benth. ex C.B. Clarke used as ingredients in the BMS poly-ingredient medicinal formulations. Furthermore, their reported phytochemicals and biological activities are also discussed in this study. Standard pharmacognostic techniques, including macroscopical and microscopical examinations of crude drugs, were employed to establish the quality control parameters for two Aster species. The physicochemical limits were determined as per the World Health Organization (WHO)-recommended guidelines and methods described in the Thai herbal pharmacopoeia. A high-performance thin-layer liquid chromatography (HPTLC) was used to develop a comparative chromatogram/phytochemical fingerprint for the crude extracts obtained from two Aster species. A literature review was conducted to record their isolated phytochemicals and biological activities. Two Aster species possess macro- and microscopic features such as colour, appearance, and shape. Physicochemical analysis of crude drugs from two Aster species including HPTLC fingerprinting of their methanol crude extracts also yielded adequate data to differentiate and confirm two Aster species before adding them to the BSM poly-ingredient medicinal formulations. From the literature review, only A. flaccidus was found to be studied for its phytochemical constituents, whereby 11 pure compounds were isolated from aerial parts and roots. The current study revealed distinct species-specific distinguishing features, including ecological adaptation, micromorphology, anatomy, physicochemical values, HPTLC chromatograms. These parameters can be used to authenticate the species identity and prevent adulterations, thereby improving the quality and safety of BSM formulations.

Approaches, Strategies and Procedures for Identifying Anti-Inflammatory Drug Lead Molecules from Natural Products.

Natural products (NPs) have played a vital role in human survival for millennia, particularly for their medicinal properties. Many traditional medicine practices continue to utilise crude plants and animal products for treating various diseases, including inflammation. In contrast, contemporary medicine focuses more on isolating drug-lead compounds from NPs to develop new and better treatment drugs for treating inflammatory disorders such as inflammatory bowel diseases. There is an ongoing search for new drug leads as there is still no cure for many inflammatory conditions. Various approaches and technologies are used in drug discoveries from NPs. This review comprehensively focuses on anti-inflammatory small molecules and describes the key strategies in identifying, extracting, fractionating and isolating small-molecule drug leads. This review also discusses the (i) most used approaches and recently available techniques, including artificial intelligence (AI), (ii) machine learning, and computational approaches in drug discovery; (iii) provides various animal models and cell lines used in in-vitro and in-vivo assessment of the anti-inflammatory potential of NPs.