Boswellic Acids: A Critical Appraisal of Their Therapeutic and Nutritional Benefits in Chronic Inflammatory Diseases.

BACKGROUND: In the last few decades, it has been largely perceived that the factors affecting the immune system and its varying pathways lead to the pathological progression of inflammation and inflammatory conditions. Chronic inflammation also contributes to common diseases, such as diabetes mellitus, ischemic heart disease, cancer, chronic renal inflammatory disease, non-alcoholic fatty hepat-ic disease, autoimmune diseases and neurodegenerative diseases. OBJECTIVE: Interestingly, plant sources and secondary metabolites from plants have been increasingly employed in managing acute and chronic inflammatory diseases for centuries. Boswellic acids are pentacyclic triterpenoidal moieties obtained from the oleo gum resin of different Boswellia species. METHODS: Detailed data was collected revealing the anti-inflammatory potential of Boswellic acids through various databases. RESULT: These are pharmacologically active agents that possess promising anti-inflammatory, anti-arthritic, antirheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, and anti-microbial effects. CONCLUSION: Boswellic acids have been in use since ancient times primarily to treat acute and chronic inflammatory diseases. This review discusses the various mechanisms underlying the inflammatory process and the necessity of such natural products as a medication to treat inflammatory diseases. In addition, a discussion has also been extended to understand the primary targets involved in inflammation. The review further explores the therapeutic potential of boswellic acids in.

In vitro anti-cancer activity of a polyherbal preparation, VEDICINALS®9, against A549 human lung adenocarcinoma cells.

PURPOSE: Non-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year survival rate of NSCLC is extremely low (<20%). This underlines the necessity of more effective therapeutic alternatives. In this context, plant-derived extracts and bioactive molecules extracted from plants, known collectively as phytoceuticals, represent an extremely variegated source of bioactive compounds with potent anticancer potential. In the present study, we tested the in vitro anticancer activity of a polyherbal preparation, VEDICINALS®9, containing nine different bioactive principles extracted by medicinal plants. METHODS: The anticancer activity of VEDICINALS®9 was investigated by measuring its impact on A549 human NSCLC cell proliferation (MTT assay and trypan blue staining), migration (wound healing assay and transwell chamber assay) and by measuring the impact on the expression of cancer-related proteins (Human XL Oncology Protein Array). RESULTS: We show that VEDICINALS®9 at a concentration of 0.2% v/v has potent anticancer effect, significantly inhibiting A549 cell proliferation and migration. Mechanistically, this was achieved by downregulating the expression of proteins involved in cancer cell proliferation (Axl, FGF basic, enolase 2, progranulin, survivin) and migration (Dkk-1, cathepsins B and D, BCL-x, amphiregulin, CapG, u-plasminogen activator). Furthermore, treatment with VEDICINALS®9 resulted in increased expression of the oncosuppressor protein p53 and of the angiogenesis inhibitor endostatin. CONCLUSIONS: Taken together, our results provide proof of principle of the potent anticancer activity of the polyherbal preparation VEDICINALS®9, highlighting its enormous potential as an alternative or adjuvant therapy for lung cancer.

Agarwood Oil Nanoemulsion Attenuates Cigarette Smoke-Induced Inflammation and Oxidative Stress Markers in BCi-NS1.1 Airway Epithelial Cells.

Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory respiratory disease characterized by frequent exacerbations and symptoms such as cough and wheezing that lead to irreversible airway damage and hyperresponsiveness. The primary risk factor for COPD is chronic cigarette smoke exposure, which promotes oxidative stress and a general pro-inflammatory condition by stimulating pro-oxidant and pro-inflammatory pathways and, simultaneously, inactivating anti-inflammatory and antioxidant detoxification pathways. These events cause progressive damage resulting in impaired cell function and disease progression. Treatments available for COPD are generally aimed at reducing the symptoms of exacerbation. Failure to regulate oxidative stress and inflammation results in lung damage. In the quest for innovative treatment strategies, phytochemicals, and complex plant extracts such as agarwood essential oil are promising sources of molecules with antioxidant and anti-inflammatory activity. However, their clinical use is limited by issues such as low solubility and poor pharmacokinetic properties. These can be overcome by encapsulating the therapeutic molecules using advanced drug delivery systems such as polymeric nanosystems and nanoemulsions. In this study, agarwood oil nanoemulsion (agarwood-NE) was formulated and tested for its antioxidant and anti-inflammatory potential in cigarette smoke extract (CSE)-treated BCi-NS1.1 airway basal epithelial cells. The findings suggest successful counteractivity of agarwood-NE against CSE-mediated pro-inflammatory effects by reducing the expression of the pro-inflammatory cytokines IL-1α, IL-1ß, IL-8, and GDF-15. In addition, agarwood-NE induced the expression of the anti-inflammatory mediators IL-10, IL-18BP, TFF3, GH, VDBP, relaxin-2, IFN-γ, and PDGF. Furthermore, agarwood-NE also induced the expression of antioxidant genes such as GCLC and GSTP1, simultaneously activating the PI3K pro-survival signalling pathway. This study provides proof of the dual anti-inflammatory and antioxidant activity of agarwood-NE, highlighting its enormous potential for COPD treatment.

Vitamin D-A prominent immunomodulator to prevent COVID-19 infection.

COVID-19 remains a life-threatening infectious disease worldwide. Several bio-active agents have been tested and evaluated in an effort to contain this disease. Unfortunately, none of the therapies have been successful, owing to their safety concerns and the presence of various adverse effects. Various countries have developed vaccines as a preventive measure; however, they have not been widely accepted as effective strategies. The virus has proven to be exceedingly contagious and lethal, so finding an effective treatment strategy has been a top priority in medical research. The significance of vitamin D in influencing many components of the innate and adaptive immune systems is examined in this study. This review aims to summarize the research on the use of vitamin D for COVID-19 treatment and prevention. Vitamin D supplementation has now become an efficient option to boost the immune response for all ages in preventing the spread of infection. Vitamin D is an immunomodulator that treats infected lung tissue by improving innate and adaptive immune responses and downregulating the inflammatory cascades. The preventive action exerted by vitamin D supplementation (at a specific dose) has been accepted by several observational research investigations and clinical trials on the avoidance of viral and acute respiratory dysfunctions. To assess the existing consensus about vitamin D supplementation as a strategy to treat and prevent the development and progression of COVID-19 disease, this review intends to synthesize the evidence around vitamin D in relation to COVID-19 infection.

Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases.

Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.

Nutraceuticals and COVID-19: A mechanistic approach toward attenuating the disease complications.

Nutraceuticals have emerged as potential compounds to attenuate the COVID-19 complications. Precisely, these food additives strengthen the overall COVID treatment and enhance the immunity of a person. Such compounds have been used at a large scale, in almost every household due to their better affordability and easy access. Therefore, current research is focused on developing newer advanced formulations from potential drug candidates including nutraceuticals with desirable properties viz, affordability, ease of availability, ease of administration, stability under room temperature, and potentially longer shelf-lives. As such, various nutraceutical-based products such as compounds could be promising agents for effectively managing COVID-19 symptoms and complications. Most importantly, regular consumption of such nutraceuticals has been shown to boost the immune system and prevent viral infections. Nutraceuticals such as vitamins, amino acids, flavonoids like curcumin, and probiotics have been studied for their role in the prevention of COVID-19 symptoms such as fever, pain, malaise, and dry cough. In this review, we have critically reviewed the potential of various nutraceutical-based therapeutics for the management of COVID-19. We searched the information relevant to our topic from search engines such as PubMed and Scopus using COVID-19, nutraceuticals, probiotics, and vitamins as a keyword. Any scientific literature published in a language other than English was excluded. PRACTICAL APPLICATIONS: Nutraceuticals possess both nutritional values and medicinal properties. They can aid in the prevention and treatment of diseases, as well as promote physical health and the immune system, normalizing body functions, and improving longevity. Recently, nutraceuticals such as probiotics, vitamins, polyunsaturated fatty acids, trace minerals, and medicinal plants have attracted considerable attention and are widely regarded as potential alternatives to current therapeutic options for the effective management of various diseases, including COVID-19.

Unravelling the Therapeutic Potential of Nano-Delivered Functional Foods in Chronic Respiratory Diseases.

Chronic inflammation of the respiratory tract is one of the most concerning public health issues, as it can lead to chronic respiratory diseases (CRDs), some of which are more detrimental than others. Chronic respiratory diseases include chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and pulmonary fibrosis. The conventional drug therapies for the management and treatment of CRDs only address the symptoms and fail to reverse or recover the chronic-inflammation-mediated structural and functional damage of the respiratory tract. In addition, the low efficacy and adverse effects of these drugs have directed the attention of researchers towards nutraceuticals in search of potential treatment strategies that can not only ameliorate CRD symptoms but also can repair and reverse inflammatory damage. Hence, there is a growing interest toward investigating the medicinal benefits of nutraceuticals, such as rutin, curcumin, zerumbone, and others. Nutraceuticals carry many nutritional and therapeutic properties, including anti-inflammatory, antioxidant, anticancer, antidiabetic, and anti-obesity properties, and usually do not have as many adverse effects, as they are naturally sourced. Recently, the use of nanoparticles has also been increasingly studied for the nano drug delivery of these nutraceuticals. The discrete size of nanoparticles holds great potential for the level of permeability that can be achieved when transporting these nutraceutical compounds. This review is aimed to provide an understanding of the use of nutraceuticals in combination with nanoparticles against CRDs and their mechanisms involved in slowing down or reversing the progression of CRDs by inhibiting pro-inflammatory signaling pathways.

Stinging Nettle (Urtica dioica L.): Nutritional Composition, Bioactive Compounds, and Food Functional Properties.

Stinging nettle (Urtica dioica L., Urticaceae) is commonly found in Asia, Africa, and Europe and has a long history of being used as food and traditional medicine. Recently, this plant is gaining attention as a highly nutritious food, where fresh leaves are dried and used as powder or in other forms. Leaves are rich in many bioactive compounds. This review aims to cover the traditional uses in food and medicine, as well as its nutritional composition, including its bioactive chemical constituents and reported food functional activities. Various bioactive chemical constituents have been isolated from stinging nettle to date, such as flavonoids, phenolic acids, amino acid, carotenoids, and fatty acids. Stinging nettle extracts and its compounds, such as rutin, kaempferol, and vitamin A, are also used for their nutritional properties and as anti-inflammatory and antioxidant agents. Future studies should focus on the proper formulation and stability testing of the functional foods containing stinging nettle and their detailed activities in clinical studies.

Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma.

Asthma is a chronic inflammatory disease primarily characterized by inflammation and reversible bronchoconstriction. It is currently one of the leading causes of morbidity and mortality in the world. Oxidative stress further complicates the pathology of the disease. The current treatment strategies for asthma mainly involve the use of anti-inflammatory agents and bronchodilators. However, long-term usage of such medications is associated with severe adverse effects and complications. Hence, there is an urgent need to develop newer, novel, and safe treatment modalities for the management of asthma. This has therefore prompted further investigations and detailed research to identify and develop novel therapeutic interventions from potent untapped resources. This review focuses on the significance of oxidative stressors that are primarily derived from both mitochondrial and non-mitochondrial sources in initiating the clinical features of asthma. The review also discusses the biological scavenging system of the body and factors that may lead to its malfunction which could result in altered states. Furthermore, the review provides a detailed insight into the therapeutic role of nutraceuticals as an effective strategy to attenuate the deleterious effects of oxidative stress and may be used in the mitigation of the cardinal features of bronchial asthma.

Rediscovering the Therapeutic Potential of Agarwood in the Management of Chronic Inflammatory Diseases.

The inflammatory response is a central aspect of the human immune system that acts as a defense mechanism to protect the body against infections and injuries. A dysregulated inflammatory response is a major health concern, as it can disrupt homeostasis and lead to a plethora of chronic inflammatory conditions. These chronic inflammatory diseases are one of the major causes of morbidity and mortality worldwide and the need for them to be managed in the long term has become a crucial task to alleviate symptoms and improve patients' overall quality of life. Although various synthetic anti-inflammatory agents have been developed to date, these medications are associated with several adverse effects that have led to poor therapeutic outcomes. The hunt for novel alternatives to modulate underlying chronic inflammatory processes has unveiled nature to be a plentiful source. One such example is agarwood, which is a valuable resinous wood from the trees of Aquilaria spp. Agarwood has been widely utilized for medicinal purposes since ancient times due to its ability to relieve pain, asthmatic symptoms, and arrest vomiting. In terms of inflammation, the major constituent of agarwood, agarwood oil, has been shown to possess multiple bioactive compounds that can regulate molecular mechanisms of chronic inflammation, thereby producing a multitude of pharmacological functions for treating various inflammatory disorders. As such, agarwood oil presents great potential to be developed as a novel anti-inflammatory therapeutic to overcome the drawbacks of existing therapies and improve treatment outcomes. In this review, we have summarized the current literature on agarwood and its bioactive components and have highlighted the potential roles of agarwood oil in treating various chronic inflammatory diseases.

Investigating the Links between Lower Iron Status in Pregnancy and Respiratory Disease in Offspring Using Murine Models.

Maternal iron deficiency occurs in 40-50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma. A low iron diet during pregnancy further increases these major disease features in offspring with experimental asthma. Importantly, a low iron diet increases neutrophilic inflammation, which is indicative of more severe disease, in asthma. Together, our data demonstrate that lower dietary iron and systemic deficiency during pregnancy can lead to physiological, immunological and anatomical changes in the lungs and airways of offspring that predispose to greater susceptibility to respiratory disease. These findings suggest that correcting iron deficiency in pregnancy using iron supplements may play an important role in preventing or reducing the severity of respiratory disease in offspring. They also highlight the utility of experimental models for understanding how iron status in pregnancy affects disease outcomes in offspring and provide a means for testing the efficacy of different iron supplements for preventing disease.

Recent Advances in Chronotherapy Targeting Respiratory Diseases.

Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h oscillation (sleep-wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual's circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.

Genus Blepharis (Acanthaceae): A review of ethnomedicinally used species, and their phytochemistry and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Blepharis is an Afro-Asiatic genus belonging to the family Acanthaceae. It comprises about 126 species that occur in arid and semi-arid habitats. Some species of Blepharis are used in traditional medicines in different countries mainly for their anti-inflammatory, wound healing activities along with treatment of gastrointestinal disorders and bone fractures. AIM OF THE REVIEW: The present review aims to collate and analyze the available data and information on distribution, traditional uses, chemical constituents and pharmacological activities of Blepharis. METHODS: Scientific information of genus Blepharis was retrieved from the online bibliographic databases such as MEDLINE/PubMed, SciFinder, Web of Science and Google Scholar and secondary resources including books and proceedings. RESULTS: Seven species of Blepharis were found to be reported frequently as useful in folklore in African and Asian countries. B. maderaspatensis was found to be widely used in Indian traditional medicines whereas the B. ciliaris and B. edulis were common in folklore of Egypt, Jordan, and Arabia. Active phytochemicals of Blepharis are flavonoids from B. ciliaris, alkaloids from B. sindica, phenolic acid derivatives, and phytosterols, and derivatives of hydroxamic acids from B. edulis resulted in possessing diverse biological properties such as anti-microbial, anti-inflammatory, and anti-cancer. CONCLUSIONS: Various species of Blepharis were found to be used in traditional medicine systems in African and Asian countries. Few of these species were studied for their bioactive chemical constituents however the activity guided isolation studies are not performed. Similarly, detailed pharmacological studies in animal models to explore their mechanism of action are also not reported. Future studies should focus on these aspects related to the medicinally used species of Blepharis. The detailed and comprehensive comparative analysis presented here gives valuable information of the currently used Blepharis species and pave the way to investigate other useful species of Blepharis pertaining to ethnobotany, phytochemistry and discovery of new drugs.

Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective.

The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.

Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin.

The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from their significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.

Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.

Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.

Crucial role for lung iron level and regulation in the pathogenesis and severity of asthma.

Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma.We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild-moderate asthma patients and correlate with lower forced expiratory volume in 1 s (FEV1). Conversely, iron-loaded cell numbers were increased in BAL in these patients and with lower FEV1/forced vital capacity (FVC) ratio. The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 (DMT1) and transferrin receptor 1 (TFR1) are increased in asthma, with TFR1 expression correlating with reduced lung function and increased Type-2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1+ macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma in vivo, including airway hyper-responsiveness (AHR) and fibrosis, and T2 inflammatory responses.Together these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic targeting of iron in the pathogenesis and severity of disease.

Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.

Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.

Molecular modulators of celastrol as the keystones for its diverse pharmacological activities.

In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.