scholarly journals In Vitro and In Vivo Effects of Flavonoids on Peripheral Neuropathic Pain

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1171 ◽  
Author(s):  
Paramita Basu ◽  
Arpita Basu
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Nerve Injury ◽  
Somatosensory System ◽  
Present Review ◽  
Common Symptom ◽  
Murine Models ◽  
Peripheral Neuropathic Pain

Neuropathic pain is a common symptom and is associated with an impaired quality of life. It is caused by the lesion or disease of the somatosensory system. Neuropathic pain syndromes can be subdivided into two categories: central and peripheral neuropathic pain. The present review highlights the peripheral neuropathic models, including spared nerve injury, spinal nerve ligation, partial sciatic nerve injury, diabetes-induced neuropathy, chemotherapy-induced neuropathy, chronic constriction injury, and related conditions. The drugs which are currently used to attenuate peripheral neuropathy, such as antidepressants, anticonvulsants, baclofen, and clonidine, are associated with adverse side effects. These negative side effects necessitate the investigation of alternative therapeutics for treating neuropathic pain conditions. Flavonoids have been reported to alleviate neuropathic pain in murine models. The present review elucidates that several flavonoids attenuate different peripheral neuropathic pain conditions at behavioral, electrophysiological, biochemical and molecular biological levels in different murine models. Therefore, the flavonoids hold future promise and can be effectively used in treating or mitigating peripheral neuropathic conditions. Thus, future studies should focus on the structure-activity relationships among different categories of flavonoids and develop therapeutic products that enhance their antineuropathic effects.

scholarly journals Scyphocephalione a Isolated from the Stem Bark of Scyphocephalium Ochocoa (Myristicaceae) Attenuate Acute and Chronic Pains Through the Antiinflammatory Activity

2022 ◽  
Author(s):  
Marius Mbiantcha ◽  
Raymond Tchouya Guy Feuya ◽  
William Nana Yousseu ◽  
Donatien Albert Atsamo ◽  
Hibrahim Foundikou ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Protein Denaturation ◽  
Cancer Drug ◽  
Cytotoxic Activities ◽  
Second Phase ◽  
Peripheral Neuropathic Pain ◽  
Anti Cancer ◽  
Anti Inflammatory

Abstract Abstract In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound isolated from Scyphocephalium ochocoa (Myristicaceae), a medicinal plant traditionally used in African countries. Recently, an in vitro study has shown its anti-inflammatory and cytotoxic activities on MCF-7 cell line of mammary carcinoma. The purpose of the present study was to assess the in vitro anti-inflammatory and in vivo anti-nociceptive activities of Scyphocephalione A. In vitro tests were carried out on cyclooxygenase and 5-lipoxygenase activities, and on protein denaturation; while in vivo tests were performed on acute and chronic pain models. It was noticed that, Scyphocephalione A (1000 µg/ml), inhibits proteins denaturation, cyclooxygenase and 5-lipoxygenase activities respectively by 74.21%, 75.80% and 64.43%. The dose 50 mg/kg of Scyphocephalione A, inhibits acetic acid (63.43%, p<0.001) and formalin (42.12% (p<0.001) within first phase and 67.53% (p<0.001) within second phase)-induced pains. At the same dose, Scyphocephalione A significantly inhibited mechanical and heat hyperalgesia, as well as cold allodynia induced by vincristine. In addition, the compound restored haematological, biochemical and oxidative stress parameters which were altered following Vincristine administration. These results suggest that Scyphocephalione A is endowed with anti-inflammatory potential and antinociceptive properties. Therefore, Scyphocephalione A can be classified as a promising molecule for the management of peripheral neuropathic pain triggered by anti-cancer drug.

scholarly journals Tannins in the Treatment of Diabetic Neuropathic Pain: Research Progress and Future Challenges

2022 ◽  
Vol 12 ◽  
Author(s):  
Norsuhana Omar ◽  
Che Aishah Nazariah Ismail ◽  
Idris Long
Keyword(s):  
Diabetes Mellitus ◽  
Neuropathic Pain ◽  
Side Effects ◽  
Antioxidant Properties ◽  
Treatment Strategies ◽  
Research Progress ◽  
Diabetic Neuropathic Pain ◽  
Preclinical Research

Diabetes mellitus and its consequences continue to put a significant demand on medical resources across the world. Diabetic neuropathic pain (DNP) is a frequent diabetes mellitus chronic microvascular outcome. Allodynia, hyperalgesia, and aberrant or lack of nerve fibre sensation are all symptoms of DNP. These clinical characteristics will lead to worse quality of life, sleep disruption, depression, and increased mortality. Although the availability of numerous medications that alleviate the symptoms of DNP, the lack of long-term efficacy and unfavourable side effects highlight the urgent need for novel treatment strategies. This review paper systematically analysed the preclinical research on the treatment of DNP using plant phytochemicals that contain only tannins. A total of 10 original articles involved in in-vivo and in-vitro experiments addressing the promising benefits of phytochemical tannins on DNP were examined between 2008 and 2021. The information given implies that these phytochemicals may have relevant pharmacological effects on DNP symptoms through their antihyperalgesic, anti-inflammatory, and antioxidant properties; however, because of the limited sample size and limitations of the studies conducted so far, we were unable to make definitive conclusions. Before tannins may be employed as therapeutic agents for DNP, more study is needed to establish the specific molecular mechanism for all of these activities along the pain pathway and examine the side effects of tannins in the treatment of DNP.

scholarly journals Thiamine Suppresses Thermal Hyperalgesia, Inhibits Hyperexcitability, and Lessens Alterations of Sodium Currents in Injured, Dorsal Root Ganglion Neurons in Rats

2009 ◽  
Vol 110 (2) ◽  
pp. 387-400 ◽  
Author(s):  
Xue-Song Song ◽  
Zhi-Jiang Huang ◽  
Xue-Jun Song
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Dorsal Root ◽  
Thermal Hyperalgesia ◽  
B Vitamins ◽  
Drg Neurons ◽  
Na Currents

Background B vitamins can effectively attenuate inflammatory and neuropathic pain in experimental animals, while their efficacy in treating clinical pain syndromes remains unclear. To understand possible mechanisms underlying B vitamin-induced analgesia and provide further evidence that may support the clinical utility of B vitamins in chronic pain treatment, this study investigated effects of thiamine (B1) on the excitability and Na currents of dorsal root ganglion (DRG) neurons that have been altered by nerve injury. Methods Nerve injury was mimicked by chronic compression of DRG in rats. Neuropathic pain was evidenced by the presence of thermal hyperalgesia. Intracellular and patch-clamp recordings were made in vitro from intact and dissociated DRG neurons, respectively. Results (1) In vivo intraperitoneal administration of B1 (66 mg/kg/day, 10-14 doses) significantly inhibited DRG compression-induced neural hyperexcitability, in addition to suppressing thermal hyperalgesia. (2) In vitro perfusion of B1 (0.1, 1 and 10 mM) resulted in a dose-dependent inhibition of DRG neuron hyperexcitability. In addition, the DRG neurons exhibited size-dependent sensitivity to B1 treatment, i.e., the small and the medium-sized neurons, compared to the large neurons, were significantly more sensitive. (3) Both in vitro (1 mM) and in vivo application of B1 significantly reversed DRG compression-induced down-regulation of tetrodotoxin-resistant but not tetrodotoxin-sensitive Na current density in the small neurons. B1 at 1 mM also reversed the compression-induced hyperpolarizing shift of the inactivation curve of the tetrodotoxin-resistant currents and the upregulated ramp currents in small DRG neurons. Conclusion Thiamine can reduce hyperexcitability and lessen alterations of Na currents in injured DRG neurons, in addition to suppressing thermal hyperalgesia.

scholarly journals Optogenetics: Therapeutic spark in neuropathic pain

2019 ◽  
Author(s):  
Long Wang ◽  
Kang Liu
Keyword(s):  
Neuropathic Pain ◽  
Basic Concept ◽  
Somatosensory System ◽  
Fluorescent Sensors ◽  
Live Cells ◽  
Bacterial Protein ◽  
Therapeutic Applications ◽  
Near Future

Optogenetics is an emerging field, which uses light and molecular genetics to manipulate the activity of live cells by expressing light-sensitive proteins. With the discovery of bacteriorhodopsin, a light-sensitive bacterial protein, in 1971 Oesterhelt and Stoeckenius laid the pavement of optogenetics. However, the cross-integration of different disciplines is a little more than a decade old. The toolbox contains fluorescent sensors and optogenetic actuators which enable visualization of signaling events and manipulation of cellular activities, respectively. Neuropathic pain is a pain caused either by damage or disease that affects the somatosensory system. The exact mechanism for the neuropathic pain is not known, however proposed mechanisms include immune reactions, ion channel expressions, and inflammation. Current regimen for the disease provides about 50% relief for only 40-60% of patients. Recent in vivo and in vitro studies demonstrate the potential therapeutic applications of optogenetics by manipulating the activity of neurons. This review summarizes the basic concept, therapeutic applications for neuropathy and potential of optogenetics to reach from bench to bedside in the near future.

scholarly journals Scolopendra subspinipes mutilans Extract Suppresses Inflammatory and Neuropathic Pain In Vitro and In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lakkyong Hwang ◽  
Il-Gyu Ko ◽  
Jun-Jang Jin ◽  
Sang-Hoon Kim ◽  
Chang-Ju Kim ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Raw 264.7 Cells ◽  
Inflammatory Factors ◽  
Raw 264.7 ◽  
Anti Inflammatory ◽  
Scolopendra Subspinipes Mutilans

Background. Sciatic nerve injury develops from a variety of pathological causes, including traumatic injury and neuroinflammatory disorders, which are accompanied by pathological changes that have a critical impact on neuropathic pain and locomotor activity. Extracts of Scolopendra subspinipes mutilans (SSM) are used in traditional medicine for the treatment of a wide range of neuropathic diseases, including lower back pain, peripheral neuropathy, and sciatic nerve injury. Although SSM shows anti-inflammatory, antibacterial, and anticonvulsant activities, its diverse mechanisms of action remain unclear. Thus, the present study examined the effects of SSM in vitro and in vivo. Methods. To estimate the anti-inflammatory effects of SSM, inflammatory conditions were induced using lipopolysaccharide (LPS) in RAW 264.7 cells, and inflammatory-related factors were evaluated by enzyme-linked immunosorbent assay (ELISA) and western blotting analyses. Sciatic nerve crush injury (SNCI) was induced in rats using a surgical clip instrument. The effects of SSM in the SNCI model were evaluated in behavioral tests by calculating the sciatic functional index (SFI) and measuring thermal hyperalgesia sensitivity and by monitoring inflammatory factors expression in western blotting analyses. Results. We observed the anti-inflammatory effects of SSM treatment both in vitro and in vivo. The PGE2 and NO production were suppressed by SSM. Protein analyses indicated that expression of NF-κB and degradation of IκBα were suppressed by SSM treatment. In addition, the levels of iNOS, TNF-α, IL-6, and COX-2 expression were reduced by SSM treatment in RAW 264.7 cells and in the SNCI-induced animals. In behavioral studies, SSM treatment enhanced the SFI and improved the thermal sensitivity test results. Conclusions. Our results suggest that SSM suppresses the production of inflammatory factors via the NF-κB pathway and accelerates the morphological and functional recovery of the peripheral nervous system. Hence, SSM may be a useful therapeutic candidate for treatment of neuropathic pain diseases.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

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