Exploring natural antidepressants using behavioral and enzyme linked immunosorbent assays

Preclinical evaluation of natural substances for anti-depressant potential using behavioral assays

Exploring Genotoxic Potential of Herbs Commonly Used in Pakistan

Providing Scientific Evidences to the Folkloric Antidepressants of Pakistan

Phytotherapy is a very common practice in Pakistan. Literature survey exhibited lack of reports addressing toxicological actions of herbs frequently used in Pakistan. Considering this, the present study is designed to explore the systemic toxicity of herbs. To begin with, the local market, herbalists and industrial herbal products will be surveyed to identify the herbs used often by our peoples. The top three utilized herbs will be evaluated for their toxicological potential using repeated dose toxicity (food and water consumption, weight variation, hematology, blood chemistry and urinalysis) as per regulatory requirement by food and drug administration (FDA). The data obtained through this study will help protecting our peoples from the toxic effects of these herbs thereby improving their socio-economic status. Additionally, this study will reduce the burden on our health care system.

Since the beginning of human civilization, herbs have been remained an integral part of society, valued for both their culinary and medicinal properties. There is a great potential in the medicinal herbs to treat diseases, particularly those refracted to the modern medicine. World Health Organization, emphasize, particularly in the third world, where 80% of the population rely on tradition medicine, the utilization of indigenous medicinal plants in their health care system and their scientific evaluation and validation. As Hazara division and related northern areas are rich in medicinal plants and where use of traditional medicine is since time immemorial. Therefore, the Pharmacological evaluation of the local medicinal plants in order to explore the underlying mechanisms responsible for their use in the traditional medical system is the need of the time. Therefore, various plants used by the local community of Hazara division for the treatment of various cardiovascular disorders will be scientifically studied for their effects and the underlying mechanism(s). For this purpose, the plants will be selected on the basis of their Ethnopharmacological uses. The selected plants will be collected from their habitats. The shade-dried and pulverized plant material will then be subjected to extraction using suitable solvent(s). The resulting crude extracts will be phytochemically evaluated for various classes of constituents using microchemical tests and the HPLC chromatograms. Then these extracts will be screened for cardiovascular activities. The plant extracts showing good results in the preliminary pharmacological screening will be studied in detail especially the underlying mechanism(s). Moreover, the extracts will be fractionated using bioassay guided protocols and the subsequent fractions will be screened for the respective bioactivities and will also be chemically characterized. This investigation would be a valuable addition to the scientific literature of the proposed medicinal plants and may also possibly lead to identify some botanicals with combination of activities either with synergistic and or side effect neutralizing potential. 

Cancer is a life-threatening human disease affecting millions of people throughout the world (Siddiqui N., https://www.shaukatkhanum.org.pk/news-a-events/events/228.html). Mostly cancer is diagnosed at later stages especially in developing countries like Pakistan and hence it causes death to millions of humans (Siddiqui N., https://www.shaukatkhanum.org.pk/news-a-events/events/228.html). In cancer certain cellular, molecular and genetic changes occur which leads to a loss of control on cell cycle and growth (Lu et al., 2006).Most of the cancer cases in Pakistan are reported at their late stage and hence remain untreatable. The current cancer therapies are extremely expensive and out of range for majority of the people in Pakistan. Therefore, there is an urgent need to find new, novel and less expensive way of treatment for this dangerous fatal disease. Pakistan is rich in various species of medicinal plants that are used in folk medicine. However, a large number of these medicinal plants have never been scientifically investigated. Previous results showed that many natural products extract, or bioactive chemical constituents have anti-cancer activities. Those reports encourage us to search local medicinal plants that are having beneficial effects for the treatment of cancer.  To perform this study, the selected plants will be collected from their habitat and will be shade-dried or will be purchased from an authentic herbal dealer. This will be followed by pulverization. The powdered plant material will be extracted with methanol. After drying in rotary evaporator, the resulting extracts will be tested for its toxicity assay against the primary cells obtained from various organs of developmental chicks. The toxicity will also be evaluated against the non-cancerous cell lines using trypan blue exclusion method or MTT assay. Based on these assays the non-toxic extracts will be selected and its anti-cancer activity will be evaluated against breast cancer cell lines. All of the experiment will be performed in 2D and newly established 3D system. 

Liver cancer is the fifth most abundant solid cancer and in cancer-related death, which accounts for the third number worldwide. Hepatoma cell culture is a crucial system for in vitro research studies in biomedical and pharmaceutical science. However, conventional two-dimensional (2D) cell cultures could not represent the complex three-dimensional (3D) natural microenvironment of liver cancer. Especially, essential biological phenomena like adhesion, migration, gene expression, and proliferation can be more clearly reproduced by 3D culture. Currently, there is a lack of an adequate 3D culture model for studying tumor microenvironment. Therefore, engineering a suitable 3D matrix system for the Hepatoma microenvironment is a major challenge to be addressed. This will bridge between in vitro culture and in vivo tumors with the concept of applying 3 Rs Replacement, Reduction and Refinement to use animals for experiments more ethically. In the current study, a 3D scaffold system will be designed to produce hepatoma tumoroids. It is expected the postulated 3D scaffold will recapitulate the hepatoma microenvironment of hepatoma and hence it will represent the chemoresistance phenomenon to an anticancer drug that of like in vivo tumor. The possible factor involved and molecular mechanism at the genetic level will be evaluated by molecular level using PCR analysis. And the level of important genes involved in chemoresistance like interleukins (ILs), tumor necrosis factors (TNF), nuclear factor kappa-B (NF-kB), matrix metalloproteinases (MMPS), and notch signaling pathway genes will be evaluated. Level of apoptosis related genes e.g., BCL-2, BCL-xl and Bax, etc. will be also observed at the molecular level. The final strategy will be to be accomplished by inhibiting or knocking out one or more of the signaling molecule to overcome the chemoresistance face to already established drugs like 5- Fluorouracil, doxorubicin and new chemotherapeutic agents like curcumin and resveratrol. 

Alcohol addiction affects a broad range of populations and has serious socio-economic and health implications for third-world countries including Pakistan. Currently, available therapies have serious challenges regarding their safety, efficacy, and tolerability leading to a high degree of relapse. Alcohol causes significant central and peripheral neurotoxicity leading to depression, Hyperalgesia and allodynia that significantly contributes to the affective component of withdrawal and are major contributor of relapse. There is growing evidence of the role of the spino-bulbar-cerebellar pathway in the expression of hyperalgesia and allodynia. The spino-bulbar-cerebellar pathway Serotonergic and adenosinergic neuron’s role in processing and control of Alcohol withdrawal-induced hyperalgesia and as a potential drug target has not yet been explored. Recently some plant origin compounds have been documented to reverse behavioral effects of alcohol sensitization through adenosinergic and serotonergic modulation. The project aims to investigate the potential of selected natural pure Phytochemicals, with documented neuroprotective effects, on acquisition and expression of alcohol dependence using animal models focusing adenosine and serotonin turnover in spino-bulbar-cerebellar pathway.

The specific objectives are to explore the effects of various doses of selected Phytochemicals on acquisition and expression of Alcohol withdrawal syndrome, Alcohol withdrawal induced depression, Alcohol withdrawal induced hyperalgesia and Allodynia, Alcohol withdrawal induced Cognitive decline and Alcohol withdrawal induced anxiety and Alcohol withdrawal induced altered socialization using animal model of alcohol addiction. At the end of the behavioral experiments’ mice shall be sacrificed key brain areas like striatum, nucleus accumbens, Hippocampus, and spino-bulbar-cerebellar pathway shall be excised and shall be screened for changes in serotonin, adenosine, and its metabolites levels along with receptors densities using specified monoclonal antibodies.

 These phytochemicals already in use can help repurpose these new potential phytochemicals as an alternative therapy for harm reduction in alcohol addiction which is the growing, least recognized health challenge in Pakistan.

Enable Ginger

Hypertension is a multifactorial disease that spread with high rate in the world particularly in the developing countries like Pakistan. This disease leads to complications such as heart and kidney diseases, disability, stroke and organ failure. Appropriate management require many drugs therapy acting at multiple therapeutic sites. Apart from inappropriate control on the progress of hypertension, these drugs are associated with some limitations including polypharmacy, side effects, cost, availability and selectivity.  To address these challenges, globally, attempts are focused on the indigenous traditional medicines (herbal drugs) to explore them as alternate to overcome some of the major issues with the antihypertensive drugs. In the past, therapeutically important medicinal plants have played a vital role in the development of novel drugs. Efforts need to put in exploring indigenous alternative herbal drugs and the active constituents to address some of the issues like polypharmacy and cost effectiveness. Traditional herbal drugs proved to be effective alternative source; however pharmacological investigation needs to be conducted to identify the important potential therapeutic agents. Six plants, based on their therapeutic use in the management of hypertension, have been selected. These important herbal drugs includeAgrimonia eupatoria, Cichorium intybus, Rosa brunoniiLindl.,Olea ferruginea Royle, Cotoneaster acuminatus,and Maytenus royleanus. These medicinal plantswill be collected and subjected to extraction (cold maceration) with appropriate solvents. Phytochemical studies, supported by HPLC, GC/MS, will be carried out to identify different constituents and comparison studies will be carried out with standards drugs. This project will be an endeavor to investigate the pharmacological effects of these plants using animal models of hypertension. In vivo studies will be performed on the crude extracts, fractions and constituents (listed below) in different hypertensive rat models, using non-invasive method of blood pressure monitoring. It is a direct method allowing to study antihypertensive effect over a period of time. This will be followed by extensive in vitro studies to investigate the underling cardiovascular mechanisms of the antihypertensive effect. The constituents from these plants, such as agrimoniin, taraxeron, baurenylacetate, Oleuropin, ligstroside, stigmasterol and urosolic acid, will also be tested using similar procedures and protocols. The response will be measured and analyzed using high-tech integrated power Lab data acquisition system. This project is expected to come up with exciting combination of multiple antihypertensive constituents in same formulation (herbal extract). The combination of different constituents is expected having synergistic and side effect nullifying potential. A correlation will be established of these constituents with the natural herbal drug. These combinations (comparatively will be very cheaper) possible be communicated for mutual benefits with pharmaceutical industries for clinical trials in human population (next phase). The constituents can be further developed into more specific and selective agents (next phase).  

Cannot connect to Ginger Check your internet connection
or reload the browserDisable in this text fieldRephraseRephrase current sentenceEdit in Ginger×

Enable GingerCannot connect to Ginger Check your internet connection
or reload the browserDisable in this text fieldRephraseRephrase current sentenceEdit in Ginger×

Enable GingerCannot connect to Ginger Check your internet connection
or reload the browserPakistan Science Foundation, Islamabad

Disable Ginger in this text fieldDisable Ginger on this website×

Enable GingerCannot connect to Ginger Check your internet connection
or reload the browserDisable GingerRephraseRephrase with Ginger (Cmd+⌥+E)Log in to edit with GingerGinger is checking your text for mistakes...Disable Ginger in this text fieldDisable Ginger on this website×