Anti-proliferative, Pro-apoptotic, and Chemosensitizing Potential of 3-Acetyl-11-keto-ß-boswellic Acid (AKBA) Against Prostate Cancer Cells.

Prostate cancer incidences are rising worldwide at an alarming rate. Drug resistance and relapse are two major challenges in the treatment of prostate cancer. Therefore, new multimodal, safe, and effective therapeutic agents are urgently required which could effectively mitigate the menace of tumor recurrence and chemo-resistance. Plant-derived products are increasingly being utilized due to their antioxidant, antibacterial, and anti-tumor potential. In the current study, 3-acetyl-11-keto-ß-boswellic acid, a triterpenoid isolated from plant Boswellia, was utilized to ascertain its chemotherapeutic potential against human prostate cancer cells. Various in vitro assays including cell viability, nuclear staining, mitochondria potential, reactive oxygen species (ROS) generation, and quantification of apoptosis, were performed for the evaluation of the cytotoxic potential of AKBA. We observed that AKBA (10-50 µM) dose-dependently suppressed cell proliferation and caused programmed cell death in PC3 cells via both intrinsic and extrinsic pathway. Intriguingly, AKBA was also found to chemosensitize PC3 cells in synergistic combination with doxorubicin. To the best of our knowledge, this is the first study to document the synergistic chemosensitizing impact of AKBA when combined with doxorubicin in prostate cancer cells.This showcases the potential of AKBA in combinatorial therapy or adjuvant therapy for the management of prostate cancer. In sum, our results suggested that AKBA is a promising drug-like molecule against prostate cancer. Our investigation introduces a novel perspective, elucidating a previously unexplored dimension, and uncovering a compelling chemosensitizing phenomenon along with a strong synergistic effect arising from the concurrent application of these two agents.

Phytochemistry and ethnopharmacological studies of genus Cimicifuga: A systematic and comprehensive review.

ETHNOPHARMACOLOGICAL USES: Black cohosh, also known as Cimicifuga sp., is one of the most widely used ethnomedicine for the treatment of major health issues in women. Some reports show that Cimicifuga sp. exhibit anti-cancer, anti-viral, anti-microbial, anti-pyretic, and anti-inflammatory properties. PURPOSE OF THIS REVIEW: The objective of this comprehensive review is to furnish current and exhaustive knowledge pertaining to the pharmacological, phytochemical, and therapeutic properties of Cimicifuga sp. MATERIALS AND METHODS: In this review, all the available information was collected on Cimicifugasp. via computerized search using Google Scholar, PubMed, Research Gate, Sci-Hub, supplementary resources (books, government reports, and Ph.D. theses). RESULT: The phytochemical investigation on Cimicifuga sp. has shown phytoconstituents such as triterpenoid glycosides, phenylpropanoid, flavonoids, saponin, lignan, nitrogenous compounds, alkaloids, 4α-Methyl steroids and some other component like monoterpene lactones cimicifugolides A-C etc. Cimicifuga conveys a wide scope of research on in-vitro and in-vivo pharmacological potential, like anti-cancer, anti-microbial, anti-viral, anti-inflammatory, estrogenic, anti-oxidant, anti-neoplastic, anti-depressant, anti-Alzheimer, and anti-climacteric properties. CONCLUSION: This article discusses the medicinal and traditional histories of various Cimicifuga species. Because quality control and safety assessments of Cimicifuga species are currently lacking, only a limited portion of the plant may be used as medication. The majority of current research focuses on triterpene glycosides. Although there are a variety of additional molecules that may have novel biological functions, systematic investigations of these compounds are lacking. The Cimicifuga plant has to go through a lot of studies before it can be completely used in clinics as a viable medicinal contender.

Methotrexate-conjugated zinc oxide nanoparticles exert a substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

In the current study, we report the synthesis of methotrexate-conjugated zinc oxide nanoparticles (MTX-ZnONPs) and their high efficacy against lung cancer cells. Conjugation of MTX with ZnONPs was authenticated by UV-vis spectroscopy, dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). This drug-nanoconjugate also showed high drug-loading efficiency. The therapeutic efficacy of MTX-ZnONPs was further tested in vitro against A549 cells, and the results of MTT and LDH release assays showed that MTX-ZnONPs, in addition to free MTX, were efficient in exerting cytotoxic effect on A549 cells; however, the effectiveness of MTX-ZnONPs was found to be considerably enhanced at very low doses compared to that of free MTX. Moreover, ZnONPs alone significantly inhibited the cell viability of A549 cells at a much higher concentration compared to MTX-ZnONPs and MTX. Furthermore, the cytomorphology of A549 cells was characterized by cellular shrinkage and detachment from the surface in all the treatment groups. Similarly, A549 cells, in all the treatment groups, showed fragmented and condensed nuclei, indicating the initiation of apoptosis. Mitochondrial membrane potential (ψm) in A549 cells showed a gradual loss in all the treatment groups. Results of the qualitative and quantitative analyses depicted increased reactive oxygen species (ROS) levels in A549 cells. The results of the caspase activity assay showed that MTX-ZnONPs andfree MTX caused significant activation of caspase-9, -8, and -3 in A549 cells; however, the effect of MTX-ZnONPs was more profound at very low doses compared to that of free MTX. Thus, our results showed high efficacy of MTX-ZnONPs, suggesting efficient intracellular delivery of the drug by ZnONPs as nanocarriers.

Phytofabricated Nanoparticle Formulation for Cancer Treatment: A Comprehensive Review.

In recent times, nanotechnology has made significant advances in the field of cancer. The majority of chemotherapeutic drugs do not selectively target cancer cells, and they might cause side effects and damage to healthy cells, resulting in a variety of adverse effects. Having a thorough understanding of nanoparticles may improve drug targeting and administration. The nano-engineering of pharmacological and natural compounds can improve the diagnosis and treatment. Polymeric micelles, liposomes, and dendrimers are examples of innovative cancer therapeutic nano-formulations. It has been demonstrated that quantum dots, nano-suspensions, and gold nanoparticles can improve drug delivery. Nanomedicines may be delivered more effectively, focusing on cancerous cells instead of healthy tissues, which minimizes undesirable side effects and drug resistance to chemotherapeutic agents. However, limited water solubility, low stability, poor absorption, and quick metabolism limit their therapeutic effectiveness. Nanotechnology has generated unique formulations to optimise the potential use of phytochemicals in anticancer therapy. Nanocomposites can improve phytochemical solubility and bioavailability, extend their half-life in circulation, and even transport phytochemicals to specific locations. The progress in using phytochemical-based nanoparticles in cancer treatment is summarized in this paper.

Factors affecting accessibility and acceptability of voluntary counselling and testing among high risk group (HRG) for human immunodeficiency virus (HIV) in NWFP Pakistan.

OBJECTIVE: To identify the factors that affect the accessibility and acceptability of Voluntary Counselling and Testing (VCT) services among High Risk Groups for HIV in NWFP. METHODS: A cross sectional study was conducted in two districts of N.W.F.P. namely Peshawar and Abbotabad from August 2007 up till January 2008. A total of 153 participants were interviewed from high risk group by convenient sampling. The high risk group included commercial sex workers and injection drug users. Information was also gathered from in-charges of VCT centers. The data were collected in two phases, in the first phase data were collected in Peshawar while in the second phase data were collected in Abbotabad. Out of 153 respondents 102 (67%) were interviewed in Peshawar while 51 (33%) respondents were interviewed in Abbotabad. RESULTS: A total of 153 respondents were interviewed, that included commercial sex workers (123) and injection drug users (30). Mostly the participants were young with a mean age of 24 +/- 8.8 years. As far as transmission of HIV was concerned 57% reported that HIV was transmitted through sexual contact, 09% said it was transmitted by contaminated instruments and syringes and around 11% reported its transmission by eating with persons having HIV/AIDS while 04% said it was transmitted by hugging/kissing. The level of knowledge about VCT was very low and about 27% of the participants had heard about VCT center. Only a small number i.e., 16 out of 153 partipants visited VCT centres. CONCLUSIONS: The study concluded that there is lackof awareness among high risk group regarding VCT and those who have heard about VCT (27%) only a few had visited the VCT center. The awareness campaign about VCT should target communities in general and high risk group in particular.

Community mental health in Peshawar, the need to reform.

Community mental health is a neglected field in many developing countries including Pakistan. Common mental disorders are high in prevalence, particularly in women. Community mental health services are lacking in Peshawar, which faces a number of challenges owing to sociopolitical instability. The aim of this literature review is to evaluate and interpret current research relevant to community mental health reform, including a review of the evidence regarding community mental health service. A selected review of published literature was undertaken using the PubMed, PsychINFO and Cochrane Database of Systematic Reviews databases. The intervention studies included in this review demonstrate that community based mental health services closely aligned with primary care services have the potential to facilitate improvements in access to care and also improvements in mental health outcomes. It concludes that lack of proper mental health policy and non-integration of mental health in primary health care adversely affects the outcome of mental health progress in community.