Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin's multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered.

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Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.

Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.

Curcumin in Liver Diseases: A Systematic Review of the Cellular Mechanisms of Oxidative Stress and Clinical Perspective

Sepsis is one of the leading causes of deaths world-wide and yet there are no therapies available other than ICU treatment. The patient outcome is determined by a complex interplay between the pro and anti-inflammatory responses of the body i.e., a homeostatic balance between these two competing events to be achieved for the patient's recovery. The initial attempts on drug development mainly focused on controlling inflammation, however, without any tangible outcome. This was despite most deaths occurring during the immune paralysis stage of this biphasic disease. Recently, the focus has been shifting to understand immune paralysis (caused by apoptosis and by anti-inflammatory cytokines) to develop therapeutic drugs. In this review we put forth an argument for a proper understanding of the molecular basis of inflammation as well as apoptosis for developing an effective therapy.

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Sepsis: Inflammation Is a Necessary Evil.

Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation

Oxidative stress is a common denominator in the pathogenesis of many chronic diseases. Therefore, antioxidants are often used to protect cells and tissues and reverse oxidative damage. It is well known that iron metabolism underlies the dynamic interplay between oxidative stress and antioxidants in many pathophysiological processes. Both iron deficiency and iron overload can affect redox state, and these conditions can be restored to physiological conditions using iron supplementation and iron chelation, respectively. Similarly, the addition of antioxidants to these treatment regimens has been suggested as a viable therapeutic approach for attenuating tissue damage induced by oxidative stress. Notably, many bioactive plant-derived compounds have been shown to regulate both iron metabolism and redox state, possibly through interactive mechanisms. This review summarizes our current understanding of these mechanisms and discusses compelling preclinical evidence that bioactive plant-derived compounds can be both safe and effective for managing both iron deficiency and iron overload conditions.

https://www.mdpi.com/2072-6643/9/7/671/pdf

Antioxidants Mediate Both Iron Homeostasis and Oxidative Stress.

Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling.

Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress.

https://doi.org/10.1016/j.accpm.2022.101091

The combination of paravertebral block and cervical vagus nerve block applied alone for anaesthesia of open appendectomy during COVID-19


 Background

Emergence agitation (EA) is a common and challenging postoperative problem in children emerging from general anesthesia. It is associated with self-injury, increases stress on healthcare team members and postoperative maladaptive behavioral changes. However, no completely effective prevention has been found for EA. Pain is considered to be an important contributor to EA. Ultrasound-guided lumbar plexus block is a safe and effective anesthetic technique that can provide satisfactory pain relief in pediatric hip surgery. We aim to investigate the effect of ultrasound-guided lumbar plexus block on emergence agitation in children undergoing hip surgery.
Methods

This prospective, randomized, controlled study was conducted in children aged 1-6 yr undergoing elective hip surgery. Subjects were randomly assigned to receive either ultrasound-guided lumbar plexus block combined with general anesthesia (Group Block, n=60) or routine general anesthesia (Group Control, n=60). The primary outcome was the incidence of EA at 30 min after emergence from general anesthesia, assessed using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes included the incidence of severe EA, postoperative pain evaluated by the Children’s Hospital of eastern Ontario Pain Scale (CHEOPS) and the incidence of postoperative adverse complications. PAED, CHEOPS were measured at 0, 5, 10, 20, and 30 min after emergence from anesthesia.
Results

The incidence of EA was significantly lower in Group Block than in Group Control [13.3% vs. 43.3%, odds ratio (OR) 0.201, 95% confidence interval (CI) 0.082to 0.496, p<0.001]. Group Block had a lower incidence of severe EA than Group Control [3.3% vs. 18.3%, odds ratio (OR) 0.154, 95% confidence interval (CI) 0.032 to 0.727, p=0.019]. CHEOPS was lower in Group Block than in Group Control [mean (95%CI), 4.5(4.4-4.6) vs.4.9 (4.8-5.0), p<0.001].
Conclusion

Ultrasound-guided lumbar plexus block could decrease the incidence and severity of emergence agitation in children undergoing hip surgery effectively.
Trial registration:

Chinese Clinical Trial Registry: ChiCTR-INR-17011525 (30/05/2017)

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Ai-Zhong Wang

Papers

Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling.

Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress.

The combination of paravertebral block and cervical vagus nerve block applied alone for anaesthesia of open appendectomy during COVID-19

Ultrasound-Guided Lumbar Plexus Block Reduces Emergence Agitation in Children Undergoing Hip Surgery: A Prospective Randomized Controlled Trial