• 제목/요약/키워드: molecular mechanisms of pharmacological action

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Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

  • Rasul, Azhar;Zhao, Bin-Ji;Liu, Jun;Liu, Bao;Sun, Jia-Xin;Li, Jiang;Li, Xiao-Meng
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권21호
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    • pp.9049-9058
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    • 2014
  • Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is an active compound isolated from roots, stems, leaves, fruits and seeds of a variety of plants. It is well known for its pharmacological properties and has been utilized as an anti-hyperprolactinemia, anti-tumor, anti-inflammatory, neuroprotetective, analgesic and immunomodulatory agent. Recently, the anticancer activity of casticin has been extensively investigated. The resulkts showed that it exerts protective potential by targeting apoptosis, considered important for cancer therapies. In this article, our aim was to review the pharmacological and therapeutic applications of casticin with specific emphasis on its anticancer functions and related molecular mechanisms. Chemotherapeutic effects are dependent on multiple molecular pathways, which may provide a new perspective of casticin as a candidate anti-neoplastic drug. This review suggests that additional studies and preclinical trials are required to determine specific intracellular sites of action and derivative targets in order to fully understand the mechanisms of its antitumor activity and validate this compound as a medicinal agent for the prevention and treatment of various cancers.

Rediscovery of Nefopam for the Treatment of Neuropathic Pain

  • Kim, Kyung Hoon;Abdi, Salahadin
    • The Korean Journal of Pain
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    • 제27권2호
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    • pp.103-111
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    • 2014
  • Nefopam (NFP) is a non-opioid, non-steroidal, centrally acting analgesic drug that is derivative of the nonsedative benzoxazocine, developed and known in 1960s as fenazocine. Although the mechanisms of analgesic action of NFP are not well understood, they are similar to those of triple neurotransmitter (serotonin, norepinephrine, and dopamine) reuptake inhibitors and anticonvulsants. It has been used mainly as an analgesic drug for nociceptive pain, as well as a treatment for the prevention of postoperative shivering and hiccups. Based on NFP's mechanisms of analgesic action, it is more suitable for the treatment of neuropathic pain. Intravenous administration of NFP should be given in single doses of 20 mg slowly over 15-20 min or with continuous infusion of 60-120 mg/d to minimize adverse effects, such as nausea, cold sweating, dizziness, tachycardia, or drowsiness. The usual dose of oral administration is three to six times per day totaling 90-180 mg. The ceiling effect of its analgesia is uncertain depending on the mechanism of pain relief. In conclusion, the recently discovered dual analgesic mechanisms of action, namely, a) descending pain modulation by triple neurotransmitter reuptake inhibition similar to antidepressants, and b) inhibition of long-term potentiation mediated by NMDA from the inhibition of calcium influx like gabapentinoid anticonvulsants or blockade of voltage-sensitive sodium channels like carbamazepine, enable NFP to be used as a therapeutic agent to treat neuropathic pain.

Dependence Potential of Quetiapine: Behavioral Pharmacology in Rodents

  • Cha, Hye Jin;Lee, Hyun-A;Ahn, Joon-Ik;Jeon, Seol-Hee;Kim, Eun Jung;Jeong, Ho-Sang
    • Biomolecules & Therapeutics
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    • 제21권4호
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    • pp.307-312
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    • 2013
  • Quetiapine is an atypical or second-generation antipsychotic agent and has been a subject of a series of case report and suggested to have the potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive. In this study, we examined quetiapine's dependence potential and abuse liability through animal behavioral tests using rodents to study the mechanism of quetiapine. Molecular biology techniques were also used to find out the action mechanisms of the drug. In the animal behavioral tests, quetiapine did not show any positive effect on the experimental animals in the climbing, jumping, and conditioned place preference tests. However, in the head twitch and self-administration tests, the experimental animals showed significant positive responses. In addition, the action mechanism of quetiapine was found being related to dopamine and serotonin release. These results demonstrate that quetiapine affects the neurological systems related to abuse liability and has the potential to lead psychological dependence, as well.

Molecular targets of pepper as bioavailability enhancer

  • Gohil, Priyanshee;Mehta, Anita
    • Advances in Traditional Medicine
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    • 제9권4호
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    • pp.269-276
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    • 2009
  • Black pepper (family Piperaceae), is called king of spices because it is one of the oldest spice and alone accounts for about 35% of the world's total spice trade. The pepper is used in Ayurvedic medicine for the treatment of various ailments particularly neurological, broncho-pulmonary and gastrointestinal disorders. Pepper has also been reported to have various pharmacological actions but recently, it is highlighted as a bioavailability enhancer. This results in higher plasma concentration of drugs, nutrients, ions and other xenobiotics, rendering them more bioavailable for physiological as well as pharmacological actions in the body. Numerous scientific studies reported that piperine; a main bioactive compound of pepper, is responsible for its bioavailability enhancing property. It's a well known fact that pepper enhances bioavailability by inhibition of microsomal enzyme system but other mechanisms are also responsible to acts as a bioavailability enhancer. The brief overview of the mechanism of action of pepper as well as its applications as bioavailability enhancer is given in the present article.

Herbal Remedies for Combating Irradiation: a Green Anti-irradiation Approach

  • Lachumy, Subramanion Jothy;Oon, Chern Ein;Deivanai, Subramanian;Saravanan, Dharmaraj;Vijayarathna, Soundararajan;Choong, Yee Siew;Yeng, Chen;Latha, Lachimanan Yoga;Sasidharan, Sreenivasan
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권10호
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    • pp.5553-5565
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    • 2013
  • Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green anti-irradiation approach for the betterment of human beings without high cost, side effects and toxicity.

Sleep-Aids Derived from Natural Products

  • Hu, Zhenzhen;Oh, Seikwan;Ha, Tae-Woo;Hong, Jin-Tae;Oh, Ki-Wan
    • Biomolecules & Therapeutics
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    • 제26권4호
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    • pp.343-349
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    • 2018
  • Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of $GABA_A$ receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.

Neuroprotective Agents in the Intensive Care Unit -Neuroprotective Agents in ICU -

  • Panahi, Yunes;Mojtahedzadeh, Mojtaba;Najafi, Atabak;Rajaee, Seyyed Mahdi;Torkaman, Mohammad;Sahebkar, Amirhossein
    • 대한약침학회지
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    • 제21권4호
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    • pp.226-240
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    • 2018
  • Neuroprotection or prevention of neuronal loss is a complicated molecular process that is mediated by various cellular pathways. Use of different pharmacological agents as neuroprotectants has been reported especially in the last decades. These neuroprotective agents act through inhibition of inflammatory processes and apoptosis, attenuation of oxidative stress and reduction of free radicals. Control of this injurious molecular process is essential to the reduction of neuronal injuries and is associated with improved functional outcomes and recovery of the patients admitted to the intensive care unit. This study reviews neuroprotective agents and their mechanisms of action against central nervous system damages.

Systems pharmacology approaches in herbal medicine research: a brief review

  • Lee, Myunggyo;Shin, Hyejin;Park, Musun;Kim, Aeyung;Cha, Seongwon;Lee, Haeseung
    • BMB Reports
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    • 제55권9호
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    • pp.417-428
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    • 2022
  • Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network-based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound-target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in high-throughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data.

Inhibition of LPS-induced NO Production and NT-$\textsc{k}B$ Activation by a Sesquiterpene from Saussurea lappa

  • Jin, Mirim;Lee, Hwa-Jin;Ryu, Jae-Ha;Chung, Kyu-Sun
    • Archives of Pharmacal Research
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    • 제23권1호
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    • pp.54-58
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    • 2000
  • To elucidate the molecular mechanisms for the suppression of LPS-induced nitric oxide (NO) production by a dehydrocostus lactone (DL) from Saussurea lappa, we examined the preventive effect of this compound on $NF-{\kappa}B$ activation in LPS-treated RAW 264.7 macrophages and U937 human monocytic cells. The results suggest that the suppression of NO production is mediated by the inhibitory action on the i-NOS gene expression through the inactivation of $NF-{\kappa}B$ and this sesquiterpene lactone can act as a pharmacological inhibitor of the $NF-{\kappa}B$ activation.

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Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach

  • Park, Sa-Yoon;Park, Ji-Hun;Kim, Hyo-Su;Lee, Choong-Yeol;Lee, Hae-Jeung;Kang, Ki Sung;Kim, Chang-Eop
    • Journal of Ginseng Research
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    • 제42권1호
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    • pp.98-106
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    • 2018
  • Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.