An Assessment of Biological Effects of Chronic Use of Cannabis Marihuana in Human Subjects

Epidemiological studies showing a protective effect of diets rich in fruits and vegetables against cancer have focused attention on the possibility that biologically-active plant secondary metabolites exert anti-carcinogenic activity. This huge group of compounds, now collectively termed ‘phytochemicals’, provides much of the flavour and colour of edible plants and the beverages derived from them. Many of these compounds also exert anti-carcinogenic effects in animal models of cancer, and much progress has been made in defining their many biological activities at the molecular level. Such mechanisms include the detoxification and enhanced excretion of carcinogens, the suppression of inflammatory processes such as cyclooxygenase-2 expression, inhibition of mitosis and the induction of apoptosis at various stages in the progression and promotion of cancer. However, much of the research on phytochemicals has been conducted in vitro, with little regard to the bioavailability and metabolism of the compounds studied. Many phytochemicals present in plant foods are poorly absorbed by human subjects, and this fraction usually undergoes metabolism and rapid excretion. Some compounds that do exert anti-carcinogenic effects at realistic doses may contribute to the putative benefits of plant foods such as berries, brassica vegetables and tea, but further research with human subjects is required to fully confirm and quantify such benefits. Chemoprevention using pharmacological doses of isolated compounds, or the development of ‘customised’ vegetables, may prove valuable but such strategies require a full risk–benefit analysis based on a thorough understanding of the long-term biological effects of what are often surprisingly active compounds.

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The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2699-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Sidney J. Stohs ◽

C. Y. O. Chen ◽

Harry G. Preuss ◽

Sidhartha D. Ray ◽

Luke R. Bucci ◽

...

Keyword(s):

Enzymatic Hydrolysis ◽

Human Subjects ◽

Biological Effects ◽

Curcuma Longa ◽

Free Form ◽

Pharmacokinetic Studies ◽

Plasma Samples ◽

Enhanced Absorption ◽

Poor Absorption ◽

Hydrolysis Of

Abstract Background Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. Methods Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. Results Hydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. Conclusions When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. Trial registration ClinicalTrails.gov, trial identifying number NCT04103788, September 24, 2019. Retrospectively registered.

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Development, Characterization and Pharmacological Evaluation of Anti-blemish Cream Containing Herbal Oils

Recent Patents on Drug Delivery & Formulation ◽

10.2174/1872211314666200601163458 ◽

2020 ◽

Vol 14 ◽

Author(s):

Sathiya Ramu ◽

Komala Mahadevappa ◽

Radhika Muniyappa Narayanaswamy ◽

Devanand Kamnoore ◽

Ramya Lingutla ◽

...

Keyword(s):

Human Subjects ◽

Topical Administration ◽

Water Type ◽

Black Cumin ◽

Therapeutic Value ◽

Oil In Water ◽

Before And After ◽

Oecd Guideline ◽

Chronic Use ◽

Viscosity Stability

Background: Many topical agents are available in the market which interfere with pigmentation process at different levels. They are often known to cause side effects ranging from irritation to tumor over chronic use. Objective: The present study was designed to develop and characterize an antiblemish cream containing herbal oils. Methods: A herbal cream was formulated using dill, nagarmotha and black cumin oil and subjected to evaluation of its antiblemish potential against stress augmented UV-B rays induced hyperpigmentation. Topical oil in water type of cream containing 2%, 4% and 6% of each oil was formulated using herbal oils. The formulated cream was characterized for solubility, pH, particle size, grittiness, viscosity, stability, phase separation, shelf life and spreadability, and found to be stable. Acute dermal toxicity was carried out individually for dill, nagarmotha and black cumin oil according to OECD guideline 402. Hyperpigmentation was induced in all the experimental animals by stress augmented UV-B irradiation method. The animals were treated for 30 days (twice daily) with standard and test formulations by topical administration, whereas the disease group was left untreated. The skin of the animals were subjected to photographical study as well as grading for pigmentation and irritation before and after treatment. After treatment period, the serum antioxidant levels were estimated and histopathology, histochemical studies of skin were performed. Results: The animals treated with test formulations containing 2%, 4%, 6% of herbal oil showed significant improvement from pigmentation compared to disease control as it is evident in photographical biochemical, histopathological and histochemical studies. Conclusion: Thus, it was concluded that the developed antiblemish cream containing herbal oils possess significant antiblemish potential. This study necessitates further evaluations in human subjects as it could have highly positive therapeutic value in the treatment of hyperpigmentation.

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Molecular Neuroimaging in Addictive Disorders

10.1093/med/9780190681425.003.0045 ◽

2017 ◽

Author(s):

Edythe D. London ◽

Chelsea L. Robertson

Keyword(s):

Brain Function ◽

Drugs Of Abuse ◽

Human Subjects ◽

Brain Dysfunction ◽

Acute Effects ◽

Addictive Disorders ◽

Fundamental Information ◽

Nuclear Medicine Procedures ◽

Drug Abstinence ◽

Chronic Use

Molecular neuroimaging, using nuclear medicine procedures to evaluate brain function and markers for specific neurochemical systems, has substantially advanced the understanding of brain dysfunction linked to addictive disorders. Neuroimaging studies of human subjects and animal models has provided fundamental information on the neurobiology of vulnerability to addiction as well as the acute effects of drugs of abuse and the sequelae of chronic use, including the persistent states that maintain addiction and lead to relapse in those who initiate drug abstinence. A common theme that has emerged from decades of brain imaging points to frontostriatal dysfunction, which is a therapeutic target.

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Ultrastructural Changes in Three Different Mammalian Cells Following Ultraviolet Laser Irradiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100095017 ◽

1972 ◽

Vol 30 ◽

pp. 350-351

Author(s):

K. Shankar Narayan ◽

Kailash C. Gupta ◽

Tohru Okigaki

Keyword(s):

Ultraviolet Light ◽

Mammalian Cells ◽

Biological Effects ◽

Survival Rates ◽

Chinese Hamster ◽

Cell Types ◽

Differential Sensitivity ◽

Ultrastructural Changes ◽

Ultraviolet Laser

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.

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Genomic analysis of C-type lectins

Biochemical Society Symposium ◽

10.1042/bss0690059 ◽

2002 ◽

Vol 69 ◽

pp. 59-72 ◽

Cited By ~ 85

Author(s):

Kurt Drickamer ◽

Andrew J. Fadden

Keyword(s):

Biological Effects ◽

Cell Signalling ◽

Genomic Analysis ◽

Binding Activity ◽

Immunoglobulin Superfamily ◽

Carbohydrate Binding ◽

Carbohydrate Recognition ◽

Calcium Dependent ◽

Binding Domains ◽

Carbohydrate Recognition Domains

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell–cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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