This review aims to briefly discuss a short list of a broad variety of inflammatory cytokines. Numerous studies have implicated that inflammatory cytokines exert important effects with regard to various inflammatory diseases, yet the reports on their specific roles are not always consistent. They can be used as biomarkers to indicate or monitor disease or its progress, and also may serve as clinically applicable parameters for therapies. Yet, their precise role is not always clearly defined. Thus, in this review, we focus on the existing literature dealing with the biology of cytokines interleukin (IL)-6, IL-1, IL-33, tumor necrosis factor-alpha (TNF-α), IL-10, and IL-8. We will briefly focus on the correlations and role of these inflammatory mediators in the genesis of inflammatory impacts (e.g., shock, trauma, immune dysregulation, osteoporosis, and/or critical illness).

Cytokines in Inflammatory Disease.

Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including anti-proliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

/pdf/naturally-occurring-anti-cancer-compounds-shining-from-d425rwrils.pdf

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.

Triptolide and celastrol are predominantly active natural products isolated from the medicinal plant Tripterygium wilfordii Hook F. These compounds exhibit similar pharmacological activities, including anti-cancer, anti-inflammation, anti-obesity, and anti-diabetic activities. Triptolide and celastrol also provide neuroprotection and prevent cardiovascular and metabolic diseases. However, toxicity restricts the further development of triptolide and celastrol. In this review, we comprehensively review therapeutic targets and mechanisms of action, and translational study of triptolide and celastrol. We systemically discuss the structure-activity-relationship of triptolide, celastrol, and their derivatives. Furthermore, we propose the use of structural derivatives, targeted therapy, and combination treatment as possible solutions to reduce toxicity and increase therapeutic window of these potent natural products from T. wilfordii Hook F.

/pdf/a-mechanistic-overview-of-triptolide-and-celastrol-natural-41rxaerii7.pdf

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F.

Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro-inflammatory cytokine production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase-1 which catalyzes the cleavage of pro-interleukins into their active forms (including interleukin-18 [IL-18] and IL-1β). The focus of this article is to discuss the time-course and regulation of inflammasome assembly and activation during TBI and SCI and their targeting in designing therapeutic approaches. We particularly focus on the inflammasomes NLRP1 and NLRP3 which play a pivotal function during TBI and SCI in the central nervous system (CNS).

Inflammasome: its role in traumatic brain and spinal cord injury†

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(19)30044-6.pdf

Triptolide and Its Derivatives as Cancer Therapies.

Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI. SCI was performed using an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and Nissl staining. Mitochondrial dysfunction was determined by quantitative real-time polymerase chain reaction (qPCR), western blot, and detection of mitochondrial membrane potential level. Microglia/macrophage activation and astrocytic response were evaluated by immunofluorescence labeling. Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11-7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage, and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines. Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation, neutrophils infiltration, and reactive gliosis, as well as mitochondrial dysfunction. Collectively, our results demonstrate that pharmacologic suppression of NLRP3 inflammasome activation controls neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity of spinal cord damage, and improves neurological recovery after SCI. These data strongly indicate that the NLRP3 inflammasome is a vital contributor to the secondary damage of SCI in mice.

/pdf/targeting-the-nlrp3-inflammasome-to-attenuate-spinal-cord-4hx9edtc17.pdf

Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice

Randomized experimental study. To investigate the molecular mechanisms of quercetin in spinal cord injury (SCI) rats. China. One hundred female Sprague-Dawley rats were randomly assigned into four groups: sham group, SCI group, SCI+Vehicle (Veh) group, and the SCI+Quercetin (Que) group. The influences of quercetin on proinflammatory cytokine levels, histological changes and locomotion scale were estimated. SCI significantly promoted nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation and increased proinflammatory cytokine productions in the SCI group as compared with the sham group. Quercetin administration significantly decreased reactive oxygen species production, inhibited NLRP3 inflammasome activation and reduced inflammatory cytokine levels. Moreover, quercetin administration attenuated histopathology and promoted locomotion recovery. Quercetin can attenuate tissue damage and improve neurological function recovery, and the mechanism may be related to the inhibition of NLRP3 inflammasome activation.

/pdf/quercetin-suppresses-nlrp3-inflammasome-activation-and-1vacpsni71.pdf

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury.

Neuroprotective effect of asiatic acid against spinal cord injury in rats.

The biological effects of asiatic acid (AA) on spinal cord injury (SCI)-induced acute lung injury (ALI) have not been investigated. We aimed to investigate the therapeutic efficacy and molecular mechanisms of AA on SCI-induced ALI. One-hundred and fifty Sprague–Dawley rats were randomly assigned to five groups: sham, SCI, SCI + dexamethasone (Dex, 2 mg/kg), SCI + AA (30 mg/kg), and SCI + AA (75 mg/kg). The influences of AA on histologic changes, pulmonary edema, neutrophil infiltration and activation, proinflammatory cytokine production, oxidative stress, and Nrf2 and NLRP3 inflammasome protein expression were estimated. AA administration at the 30- and 75-mg/kg doses significantly attenuates lung wet-to-dry weight (W/D) ratio, pulmonary permeability index (PPI), and pulmonary histologic conditions. Furthermore, the protective effects of AA might be attributed to the reduction of neutrophil infiltration, myeloperoxidase (MPO), inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and the increase of superoxide dismutase (SOD) and catalase (CAT). Moreover, AA markedly upregulated Nrf2 levels and downregulated NLRP3 inflammasome protein expression in lung tissues. AA exhibits a protective effect on SCI-induced ALI by alleviating the inflammatory response, by inhibiting NLRP3 inflammasome activation and oxidative stress with the upregulation of Nrf2 protein levels. The use of AA may be a potential efficient therapeutic strategy for the treatment of SCI-induced ALI.

Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats

We aimed to study the anti-tumor effects of triptolide on osteosarcoma and the related molecular mechanisms. The cell viability, apoptosis portion, tumor size, tumor weight, and invasion of osteosa...

https://journals.sagepub.com/doi/pdf/10.1177/1010428317697556

Maoqiang Li

Papers

Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice

Quercetin suppresses NLRP3 inflammasome activation and attenuates histopathology in a rat model of spinal cord injury.

Neuroprotective effect of asiatic acid against spinal cord injury in rats.

Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats

Triptolide inhibits the growth of osteosarcoma by regulating microRNA-181a via targeting PTEN gene in vivo and vitro.