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1.
Surg Clin North Am ; 99(6): 1223-1235, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676060

RESUMO

Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.


Assuntos
Produtos Biológicos/administração & dosagem , Tratamento Conservador/métodos , Imunossupressores/administração & dosagem , Doenças Inflamatórias Intestinais/terapia , Produtos Biológicos/farmacologia , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Seleção de Pacientes , Recidiva , Retratamento , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
2.
Hautarzt ; 70(12): 926-933, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31712972

RESUMO

Biopharmaceuticals are pharmaceutical drug products or preparations of pharmaceutical drugs that are of biological origin or are manufactured from biological material. The spectrum of biological drugs is extensive and includes substances isolated from biological material, recombinant RNA molecules, proteins as well as full antibodies, antibody fragments or antibody-drug conjugates. The special features of the molecular properties and functions of biopharmaceuticals require a highly complex, variable structure. Due to the specificity of intended pharmacodynamic effects on a complex biological regulatory system, particularities regarding undesired effects, pharmacokinetics, and safety have to be considered both regulatory and clinical.


Assuntos
Produtos Biológicos , Produtos Biológicos/farmacologia
3.
Adv Exp Med Biol ; 1182: 1-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777013

RESUMO

Ganoderma (Lingzhi) has been used for a long time in China to prevent and treat various diseases. Accumulated studies have demonstrated that the Ganoderma modulates immune function both in vivo and in vitro. The immunomodulating effects of Ganoderma were extensive, including promoting the innate immune function, humoral immunity, and cellular immunity. In particular, G. lucidum polysaccharides may affect immune cells and immune-related cells including B and T lymphocytes, dendritic cells, macrophages, and natural killer cells, with the promotion of immune organ growth, cytokine release, and other immune regulatory functions. Furthermore, cellular and molecular immunomodulatory mechanisms, possible receptors involved, and triggered signaling pathways have also been summarized. However, whole animal experiments are still needed to further establish the mechanism of the immunomodulating effects by Ganoderma. Importantly, evidence-based clinical trials are also needed.


Assuntos
Produtos Biológicos/farmacologia , Imunomodulação , Polissacarídeos/farmacologia , Reishi/química , Animais , China , Humanos , Imunidade Celular , Imunidade Humoral , Imunidade Inata
4.
Adv Exp Med Biol ; 1182: 39-77, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777014

RESUMO

The antitumor effect of Ganoderma (Lingzhi) is closely related to immunoregulation. Based on our research and other references, this article discussed the antitumor effect of Ganoderma mediated by immunological mechanism, including promoting the function of mononuclear-macrophages and natural killers; promoting M1-type macrophage polarization vs M2-type; promoting maturation and differentiation of dendritic cells, increasing its antigen presentation, activating lymphocytes and increasing cytotoxicity of cytotoxin T lymphocyte; promoting production of cytokines; and inhibiting tumor escape from immune surveillance. Also, clinical studies with immunological indexes were reviewed.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Imunomodulação , Neoplasias/tratamento farmacológico , Reishi/química , Apresentação do Antígeno , Diferenciação Celular , Citocinas/imunologia , Células Dendríticas/imunologia , Humanos , Macrófagos/imunologia , Linfócitos T/imunologia
5.
Adv Exp Med Biol ; 1182: 79-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777015

RESUMO

The anticancer potential of Ganoderma (Lingzhi) and its extracts has been widely demonstrated, including antiproliferative and apoptosis inductive, antimetastatic, antiangiogenic, and multidrug resistance reversional activities, involving a variety of cellular and molecular mechanisms besides antitumor immunology. Intrinsic- and extrinsic-initiated apoptotic pathway in association with cell cycle arresting, telomerase inhibiting, autophagy, and oxidative stress is involved in the antiproliferative and apoptosis inductive activities of Ganoderma and its extracts. The inhibition of tumor cell adhesion, invasion, and migration by Ganoderma and its extracts involves molecular mechanisms such as AP-1, NF-κB, MMP, cadherin, ß-integrin, c-Met, FAK, EMT, and so on. Targeting the major pro-angiogenic stimulus, VEGF, and its receptor contributes to the inhibition of tumor angiogenesis by Ganoderma and its extracts. Inhibition against the ATP-dependent transmembrane drug transporter such as P-glycoprotein (P-gp) on the surface of resistant tumor cells to prevent reduction of the intracellular accumulation of anticancer drugs by pumping out the drugs plays an important role in the activities of Ganoderma and its extracts to reverse tumor cell multidrug resistance.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Neoplasias/tratamento farmacológico , Reishi/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos
6.
Adv Exp Med Biol ; 1182: 119-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777016

RESUMO

Radiation and chemotherapy are common and mainstay treatments for cancer patients. But they are also usually associated with some toxicity and side effects in most of the patients. Ganoderma (Lingzhi) is considered as a major kind of complementary/alternative medicine and used to prevent the adverse effects caused by radiation and chemotherapy. This chapter reviewed the protective effects of Ganoderma (Lingzhi) on radiation and chemotherapy, including the preventive effects on myelosuppression, intestinal injury, nephrotoxicity, cardiovascular toxicity, and other side effects. Both basic researches and clinical studies of Ganoderma (Lingzhi) in preventing side effects induced by radiation and chemotherapy were reviewed.


Assuntos
Produtos Biológicos/farmacologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Protetores contra Radiação/farmacologia , Reishi/química , Humanos
7.
Adv Exp Med Biol ; 1182: 143-157, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777017

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi) is a kind of medical mushroom with various pharmacological compounds. It has been used for clinical applications for thousands of years as a highly nutritious and significantly effective medicinal herb. Compared with its immunomodulatory effect, there are a few studies on the neuropharmacological actions of Ganoderma, and the mechanism has not been fully elucidated. As far as we know, Ganoderma regulate the central nervous system (CNS) at least in part through its immunomodulatory activity. The neuropharmacological effects of G. lucidum mainly include but not limited to sedative and hypnotic, neuroprotective, antinociceptive and analgesic, antiepileptic, and antidepressant effects. Clinical trials of G. lucidum in the patients with these disorders are still rare. To date, there are no Ganoderma-related drugs approved by the US Food and Drug Administration (FDA). In this chapter, we will summarize and elucidate recent progress of such effects of Ganoderma and its ingredients from both the preclinical and clinical points of view.


Assuntos
Produtos Biológicos/farmacologia , Fármacos do Sistema Nervoso Central/farmacologia , Reishi/química , Humanos
8.
Adv Exp Med Biol ; 1182: 159-180, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777018

RESUMO

Neurological dysfunction and death are common events leading to acute and chronic neurodegenerative diseases. Neurodegenerative disorders such as Alzheimer's and Parkinson's disease account for a significant and increasing proportion of morbidity and mortality in the developed world. Ganoderma lucidum (G. lucidum, Lingzhi), one of highly nutritious and significantly effective medicinal herbs, has been used for clinical applications for thousands of years. Several researches have shown that it has a wide range of brain damage protection, such as amelioration of Alzheimer's disease, therapeutic effect on epilepsy, and the protective effect on neural cells in stroke injury. This chapter reviews the neuroprotective effects of G. lucidum and its extracts on brain injury diseases, including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, and other neurodegenerative diseases, and the potential clinical applications.


Assuntos
Produtos Biológicos/farmacologia , Lesões Encefálicas/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Reishi/química , Humanos
9.
Adv Exp Med Biol ; 1182: 181-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777019

RESUMO

Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels and include coronary heart diseases, cerebrovascular diseases, rheumatic heart diseases, and other conditions. CVDs are one of the most major causes of morbidity and mortality around the world, taking the lives of 17.9 million people every year. Several investigations have shown the influence of Ganoderma lucidum (G. lucidum, Lingzhi) on some metabolic markers, such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), blood pressure, and oxidative damage. G. lucidum potentially reduces the risk of suffering cardiovascular diseases. Some studies found that G. lucidum prevented from heart damage in a variety of disease models, such as streptozotocin (STZ)-induced diabetic, high-fat-diet-induced diabetic, isoprenaline (ISO)-induced myocardial hypertrophy, acute ethanol-induced heart toxicity, and transverse aortic constriction (TAC) models. This chapter summarizes putative preventive and therapeutic effects of G. lucidum on cardiovascular diseases and the potential clinical use of G. lucidum involved in these effects.


Assuntos
Produtos Biológicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Reishi/química , Humanos
10.
Adv Exp Med Biol ; 1182: 201-215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777020

RESUMO

As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.


Assuntos
Produtos Biológicos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Reishi/química , Animais , Camundongos
11.
Adv Exp Med Biol ; 1182: 217-242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777021

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi) has a wide range of hepatoprotective effects. Its bioactive substances include triterpenoids, polysaccharides, sterols, steroids, peptides, and other bioactive ingredients. Based on our research and other references, this chapter discusses the hepatoprotective effects of G. lucidum in different liver diseases, including hepatocellular carcinoma, nonalcoholic liver disease, alcoholic liver disease, hepatitis B, inflammation, fibrosis, and toxicant-induced liver injury. The liver protective mechanisms of G. lucidum vary from diseases to diseases. This chapter will summarize the hepatoprotective effects of G. lucidum on different liver injury and their clinical applications.


Assuntos
Produtos Biológicos/farmacologia , Hepatopatias/tratamento farmacológico , Fígado/efeitos dos fármacos , Reishi/química , Humanos
12.
Adv Exp Med Biol ; 1182: 243-262, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777022

RESUMO

The mechanisms of kidney diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), have been intensively studied. Nonetheless, the morbidity and mortality of AKI and CKD increased in recent years. Recently, natural products have been increasingly recognized as an alternative source for treating renal diseases on account of the conventional experience and the multi-target characteristics. Ganoderma lucidum (G. lucidum, Lingzhi) has been used for centuries as nutraceuticals and alternative medicine to improve health and to treat numerous diseases. Benefiting from various biological activities, such as anti-oxidation, anti-inflammation, anti-tumor growth and metastasis, etc., G. lucidum has been proved to exhibit significant role in preventing and treating various kidney diseases. In this chapter, we review certain researches and provide comprehensive insights into the renoprotective effects of G. lucidum.


Assuntos
Produtos Biológicos/farmacologia , Nefropatias/tratamento farmacológico , Reishi/química , Humanos
13.
Adv Exp Med Biol ; 1182: 263-269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777023

RESUMO

The anti-osteoporosis effect of Ganoderma lucidum (G. lucidum, Lingzhi) is closely associated with inhibition of osteoclastogenesis in the charge of osteoclasts. This article reviewed the anti-osteoporosis effect of Ganoderma and its active components, including a kind of triterpenoids, a polysaccharide and a protein named Ling Zhi-8 (LZ-8). Triterpenoids are a kind of active compounds as candidates for the treatment of osteoporosis. Among these, ganoderic acids are currently considered as the most important and potential components, and their structure-activity relationship highlights the essential group to hamper osteoclast differentiation. The data confirmed that the active compounds isolated from triterpenoids and meroterpenoids could suppress bone resorption of osteoclast via RANKL/RANK pathway and/or its downstream signaling transduction related to ERK, JNK and p38 MAPKs, contributing to inhibition of the level of c-Fos and NFATc1, two key target genes of osteoclast for osteoclastogenesis. However, the comprehensive mechanism remains to be elucidated in the future.


Assuntos
Produtos Biológicos/farmacologia , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Reishi/química , Diferenciação Celular , Humanos , Osteoclastos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Adv Exp Med Biol ; 1182: 271-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777024

RESUMO

This article reviewed the antioxidative effect and free radical scavenging activity of Ganoderma lucidum (G. lucidum, Lingzhi). G. lucidum has apparent protective effects against the lipid peroxidation caused by a variety of factors in the brain, heart, pancreas, liver, gastrointestinal, kidney, and other vital organs. G. lucidum can significantly reduce the content of lipid peroxidation product such as malondialdehyde (MDA) and lipofuscin and can enhance the activities of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-P), and other antioxidative enzymes. In macrophages (mouse), islet cells (mouse), cerebral cortex cells (rat), pheochromocytoma cells (PC12 cells, rat), vascular endothelial cells (rat, human), and keratinocytes (human), G. lucidum has significant protective effect against the oxidant-induced oxidative damage. Antioxidative effect and free radical scavenging activity of G. lucidum on different animal models in vivo and in vitro may be related to its pharmacological mechanism of immunomodulating, antitumor, antihypertensive, hypoglycemic, brain-protective, liver-protective, cardiovascular-protective, renal-protective, and antiaging effects.


Assuntos
Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Reishi/química , Animais , Humanos , Peroxidação de Lipídeos , Camundongos , Ratos
15.
Adv Exp Med Biol ; 1182: 299-309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777025

RESUMO

Although Ganoderma (Lingzhi in Chinese) has been used as an elixir for thousands of years, its anti-aging effects still need to be clarified. Aging is related to immunoregulation, oxidation stress, and free radical product. Till now, Ganoderma exert life span elongation activities by inhibiting ROS production, lipid peroxidation, and advanced oxidation protein products; increasing production of mitochondrial electron transport complexes, SOD, CAT, GSH and GSH-Px, DPPH, and ABTS radical scavenger activities; and having immunomodulatory and antioxidant activity by increasing radical scavenging activity and ferric reducing antioxidant power. Ganoderma's anti-aging effect on human remains a mystery, and its potential mechanisms underlying anti-aging effect for its clinical application still need to be elucidated.


Assuntos
Envelhecimento/efeitos dos fármacos , Produtos Biológicos/farmacologia , Aptidão Física , Reishi/química , Antioxidantes/farmacologia , Humanos , Peroxidação de Lipídeos , Estresse Oxidativo
16.
Adv Exp Med Biol ; 1182: 311-321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777026

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi), a kind of mushroom with various bioactivities, is recently revealed to improve skin quality and treat skin diseases. Traditionally, polysaccharides and ganoderic acids have been reported as the major functional metabolites of Ganoderma possessing antioxidant and anti-inflammatory functions. Based on our research and other studies, Ganoderma extracts, such as Ganoderma polysaccharides, have been used in promoting skin wound healing, mitigating postburn infection, and preventing skin flap ischemia-reperfusion injury. Ganoderma extracts have also been used in skin care, because of their roles in skin photoaging and skin whitening. Meanwhile, the anti-inflammatory effect of Ganoderma in atopic dermatitis and cutaneous sarcoidosis is also elaborated in this chapter. Finally, the potential use of Ganoderma in skin carcinoma is introduced. In brief, the dermoprotective effect of Ganoderma will be summarized in this chapter.


Assuntos
Produtos Biológicos/farmacologia , Polissacarídeos/farmacologia , Reishi/química , Dermatopatias/tratamento farmacológico , Humanos
17.
Prog Chem Org Nat Prod ; 110: 73-97, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621011

RESUMO

Natural products have long played a leading role as direct source of drugs or as a means to inspire informed molecular design. Indeed, natural products have been biologically prevalidated as protein-binding motifs by millions of years of evolutionary pressure. Despite the tailored architectures, and the ever-growing chemistry toolbox to aid access such privileged structures, identifying the modes of action by which these molecules can be harnessed as therapeutics remains a major bottleneck in discovery chemistry. Herein, an overview of cheminformatics methods applied to the identification of modes of action of natural products is given, and a discussion of successful case studies is provided. A special focus is given to machine learning methods that may help to streamline the development of natural products into drug leads.


Assuntos
Produtos Biológicos/farmacologia , Biologia Computacional , Descoberta de Drogas , Química Farmacêutica
18.
Prog Chem Org Nat Prod ; 110: 177-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621014

RESUMO

Interference with the hERG potassium ion channel may cause cardiac arrhythmia and can even lead to death. Over the last few decades, several drugs, already on the market, and many more investigational drugs in various development stages, have had to be discontinued because of their hERG-associated toxicity. To recognize potential hERG activity in the early stages of drug development, a wide array of computational tools, based on different principles, such as 3D QSAR, 2D and 3D similarity, and machine learning, have been developed and are reviewed in this chapter. The various available prediction tools Similarity Ensemble Approach, SuperPred, SwissTargetPrediction, HitPick, admetSAR, PASSonline, Pred-hERG, and VirtualToxLab™ were used to screen a dataset of known hERG synthetic and natural product actives and inactives to quantify and compare their predictive power. This contribution will allow the reader to evaluate the suitability of these computational methods for their own related projects. There is an unmet need for natural product-specific prediction tools in this field.


Assuntos
Produtos Biológicos/farmacologia , Biologia Computacional , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Bloqueadores dos Canais de Potássio/farmacologia , Química Farmacêutica , Humanos , Aprendizado de Máquina , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade
19.
Prog Chem Org Nat Prod ; 110: 239-271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621015

RESUMO

Cheminformatics-based techniques, such as molecular modeling, docking, virtual screening, and machine learning, are well accepted for their usefulness in drug discovery and development of therapeutically relevant small molecules. Although delayed by several decades, their application in natural product research has led to outstanding findings. Combining information obtained from different sources, i.e., virtual predictions, traditional medicine, structural, biochemical, and biological data, and handling big data effectively will open up new possibilities, but also challenges in the future. Strategies and examples will be presented on how to integrate cheminformatics in pharmacognostic workflows to benefit from these two highly complementary disciplines toward streamlining experimental efforts. While considering their limits and pitfalls and by exploiting their potential, computer-aided strategies should successfully guide future studies and thereby augment our knowledge of bioactive natural lead structures.


Assuntos
Produtos Biológicos/farmacologia , Biologia Computacional , Modelos Moleculares , Química Farmacêutica , Descoberta de Drogas , Aprendizado de Máquina
20.
Medicine (Baltimore) ; 98(39): e17326, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574867

RESUMO

BACKGROUND: Diabetes mellitus type 2 (DM2) is a chronic disease of significant prevalence causing hyperglycemia and several comorbidities. Evidences highlight the performance of non - protein bioactive compounds found in vegetables in the control of hyperglycemia. This study describes a protocol of a systematic review, which analyzes the action of proteins and bioactive peptides of plants in DM2. METHODS: The Preferred Reporting Items guide this protocol for Systematic Reviews and Meta-Analyzes Protocols (PRISMA-P) was used. The databases that will be used for searching will be PubMed, ScienceDirect, Scopus, Web of Science, EMBASE, and Virtual Health Library, Brazil (VHL). Studies that use bioactive proteins and peptides of vegetal origin in DM2 will be included in the systematic review. The studies will be identified using clinical parameters and the effect on insulin resistance. The characteristics of the studies as control groups, test substance, dosage, intervention time, and the main results will be described. Selection of studies, data extraction, and methodological quality assessment will be performed independently by two experienced reviewers. RESULTS: This protocol will be the basis for a systematic review identifying the mechanism of action of plant proteins and peptides in type 2 diabetes mellitus. CONCLUSION: Systematic reviews from this protocol will provide support for the construction of researches that analyze the effect of plant bioactive proteins and peptides on the control of hyperglycemia and how these molecules act in the control of DM2. PROSPERO REGISTRATION NUMBER: CRD42019110956.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Proteínas de Vegetais Comestíveis/farmacologia , Produtos Biológicos/farmacologia , Humanos , Resultado do Tratamento
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