Wogonin and its analogs for the prevention and treatment of cancer: A systematic review.

The medicinal plant Scutellaria baicalensis, commonly known as Chinese skullcap or Huang-Qin, has been used as a traditional medicine for several thousand years. The roots of this plant contain bioactive compounds, such as wogonin (WOG), wogonoside, baicalein, and baicalin. The aim of this article is to evaluate the therapeutic potential and mechanisms of action of WOG against different cancers. Numerous in vitro and in vivo studies have revealed that WOG exerts immense therapeutic potential against bladder cancer, breast cancer, cholangiocarcinoma, cervical cancer, colorectal cancer, gallbladder cancer, gastric cancer, glioblastoma, head and neck cancer, hepatic cancer, leukemia, lung cancer, lymphoma, melanoma, multiple myeloma, neuroblastoma, osteosarcoma, ovarian cancer, pancreatic cancer, prostate cancer, and renal cancer by regulating various cell signaling pathways. WOG, in combination with established chemotherapeutic drugs, improves the efficacy of treatment and lowers toxicity. Nevertheless, human trials are warranted to validate these findings. Numerous preclinical studies, combined with an extensive margin of safety and no severe side effects, underscore WOG's therapeutic potential as an anticancer drug. These studies propound the use of WOG as a potential anticancer candidate; however, further high-quality studies are required to firmly establish the clinical efficacy of WOG for the prevention and treatment of human malignancies.

Current clinical developments in curcumin-based therapeutics for cancer and chronic diseases.

The last decade has seen an unprecedented rise in the prevalence of chronic diseases worldwide. Different mono-targeted approaches have been devised to treat these multigenic diseases, still most of them suffer from limited success due to the off-target debilitating side effects and their inability to target multiple pathways. Hence a safe, efficacious, and multi-targeted approach is the need for the hour to circumvent these challenging chronic diseases. Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, has been under intense scrutiny for its wide medicinal and biological properties. Curcumin is known to manifest antibacterial, antiinflammatory, antioxidant, antifungal, antineoplastic, antifungal, and proapoptotic effects. A plethora of literature has already established the immense promise of curcuminoids in the treatment and clinical management of various chronic diseases like cancer, cardiovascular, metabolic, neurological, inflammatory, and infectious diseases. To date, more than 230 clinical trials have opened investigations to understand the pharmacological aspects of curcumin in human systems. Still, further randomized clinical studies in different ethnic populations warrant its transition to a marketed drug. This review summarizes the results from different clinical trials of curcumin-based therapeutics in the prevention and treatment of various chronic diseases.

Synthesis of new selective cytotoxic ricinine analogues against oral squamous cell carcinoma.

Sixteen new analogues were synthesized from ricinine and tested alongside with seven known analogues for their cytotoxic activity against oral cancer (SAS cells) and normal epithelial cells (L132 cells). In contrast to 5-FU, the synthesized ricinine analogues did not show toxicity to normal cells. However, some of them inhibited the proliferation of oral cancer cells at 25 µM as evident from the MTT assay results. Ricinine analogue (19) was shown to be the most active derivative (69.22% inhibition). Potential targets involved in the oral cancer inhibitory activity of compound 19 were investigated using in-silico studies and western blot analysis. PTP1B was predicted to be a target for ricinine using reverse docking approach. This prediction was confirmed by western blot analysis that revealed the downregulation of PTP1B protein by compound 19. Moreover, it showed downregulation of COX-2 which is also extensively expressed in oral cancer.

Diosgenin, a steroidal saponin, and its analogs: Effective therapies against different chronic diseases.

BACKGROUND: Chronic diseases are a major cause of mortality worldwide, and despite the recent development in treatment modalities, synthetic drugs have continued to show toxic side effects and development of chemoresistance, thereby limiting their application. The use of phytochemicals has gained attention as they show minimal side effects. Diosgenin is one such phytochemical which has gained importance for its efficacy against the life-threatening diseases, such as cardiovascular diseases, cancer, nervous system disorders, asthma, arthritis, diabetes, and many more. AIM: To evaluate the literature available on the potential of diosgenin and its analogs in modulating different molecular targets leading to the prevention and treatment of chronic diseases. METHOD: A detailed literature search has been carried out on PubMed for gathering information related to the sources, biosynthesis, physicochemical properties, biological activities, pharmacokinetics, bioavailability and toxicity of diosgenin and its analogs. KEY FINDINGS: The literature search resulted in many in vitro, in vivo and clinical trials that reported the efficacy of diosgenin and its analogs in modulating important molecular targets and signaling pathways such as PI3K/AKT/mTOR, JAK/STAT, NF-κB, MAPK, etc., which play a crucial role in the development of most of the diseases. Reports have also revealed the safety of the compound and the adaptation of nanotechnological approaches for enhancing its bioavailability and pharmacokinetic properties. SIGNIFICANCE: Thus, the review summarizes the efficacy of diosgenin and its analogs for developing as a potent drug against several chronic diseases.

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties.

According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.

Potential of guggulsterone, a farnesoid X receptor antagonist, in the prevention and treatment of cancer.

Cancer is one of the most dreadful diseases in the world with a mortality of 9.6 million annually. Despite the advances in diagnosis and treatment during the last couple of decades, it still remains a serious concern due to the limitations associated with currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. The importance of medicinal plants as primary healthcare has been well-known from time immemorial against various human diseases, including cancer. Commiphora wightii that belongs to Burseraceae family is one such plant which has been used to cure various ailments in traditional systems of medicine. This plant has diverse pharmacological properties such as antioxidant, antibacterial, antimutagenic, and antitumor which mostly owes to the presence of its active compound guggulsterone (GS) that exists in the form of Z- and E-isomers. Mounting evidence suggests that this compound has promising anticancer activities and was shown to suppress several cancer signaling pathways such as NF-κB/ERK/MAPK/AKT/STAT and modulate the expression of numerous signaling molecules such as the farnesoid X receptor, cyclin D1, survivin, caspases, HIF-1α, MMP-9, EMT proteins, tumor suppressor proteins, angiogenic proteins, and apoptotic proteins. The current review is an attempt to summarize the biological activities and diverse anticancer activities (both in vitro and in vivo) of the compound GS and its derivatives, along with its associated mechanism against various cancers.

Is curcumin bioavailability a problem in humans: lessons from clinical trials.

Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principal component of turmeric is curcumin and its efficacy has been advocated in various in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem. Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated the pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies. Expert opinion: The therapeutic potential of curcumin, as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailability in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin, in combination with other compounds or as formulations, has shown enhanced bioavailability. Hence, bioavailability is not a problem in the curcumin-mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases.

Chronic diseases, inflammation, and spices: how are they linked?

Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc. Numerous lines of evidence suggest that the aforementioned risk factors induced cancer through chronic inflammation. First, transcription factors NF-κB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-κB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-κB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors. Therefore, targeting these pathways may provide opportunities for both prevention and treatment of cancer and other chronic diseases. We will discuss in this review the potential of various dietary agents such as spices and its components in the suppression of inflammatory pathways and their roles in the prevention and therapy of cancer and other chronic diseases. In fact, epidemiological studies do indicate that cancer incidence in countries such as India where spices are consumed daily is much lower (94/100,000) than those where spices are not consumed such as United States (318/100,000), suggesting the potential role of spices in cancer prevention.

Therapeutic potential of gambogic acid, a caged xanthone, to target cancer.

Natural compounds have enormous biological and clinical activity against dreadful diseases such as cancer, as well as cardiovascular and neurodegenerative disorders. In spite of the widespread research carried out in the field of cancer therapeutics, cancer is one of the most prevalent diseases with no perfect treatment till date. Adverse side effects and the development of chemoresistance are the imperative limiting factors associated with conventional chemotherapeutics. For this reason, there is an urgent need to find compounds that are highly safe and efficacious for the prevention and treatment of cancer. Gambogic acid (GA) is a xanthone structure extracted from the dry, brownish gamboge resin secreted from the Garcinia hanburyi tree in Southeast Asia and has inherent anti-cancer properties. In this review, the molecular mechanisms underlying the targets of GA that are liable for its effective anti-cancer activity are discussed that reveal the potential of GA as a pertinent candidate that can be appropriately developed and designed into a capable anti-cancer drug.