Investigating the Therapeutic Potential of Plants and Plant-Based Medicines: Relevance to Antioxidant and Neuroprotective Effects.

Oxidative stress is a common characteristic of psychiatric, neurological, and neurodegenerative disorders. Therefore, compounds that are neuroprotective and reduce oxidative stress may be of interest as novel therapeutics. Phenolic, flavonoid and anthocyanin content, ORAC and DPPH free radical scavenging, and Cu2+ and Fe2+ chelating capacities were examined in variations (fresh/capsule) of Queen Garnet plum (QGP, Prunus salicina), black pepper (Piper nigrum) clove (Syzygium aromaticum), elderberry (Sambucus nigra), lemon balm (Melissa officinalis) and sage (Salvia officinalis), plus two blends (Astralagus membranaceus-lemon balm-rich, WC and R8). The ability of samples to prevent and treat H2O2-induced oxidative stress in SH-SY5Y cells was investigated. Pre-treatment with WC, elderberry, QGP, and clove prevented the oxidative stress-induced reduction in cell viability, demonstrating a neuroprotective effect. Elderberry increased cell viability following oxidative stress induction, demonstrating treatment effects. Clove had the highest phenolic and flavonoid content, DPPH, and Cu2+ chelating capacities, whereas QGP and elderberry were highest in anthocyanins. Black pepper had the highest ORAC and Fe2+ chelating capacity. These findings demonstrate that plant extracts can prevent and treat oxidative stress-induced apoptosis of neuron-like cells in vitro. Further research into phytochemicals as novel therapeutics for oxidative stress in the brain is needed.

Rod-like hybrid nanomaterial with tumor targeting and pH-responsive for cancer chemo/photothermal synergistic therapy.

The development of chemo/photothermal nanotherapeutic systems with excellent photothermal performance, stable drug loading, tumor targeting and strong membrane penetration still remains a challenge. To address this problem, herein a rod-like nanocomposite system (AuNR@FA-PR/PEG) forming from folic acid (FA) terminated carboxylated cyclodextrin (CD) pseudopolyrotaxane (FA-PR) and polyethylene glycol (PEG) modifying gold nanorods (AuNR) was reported. Cisplatin (CDDP) was loaded in AuNR@FA-PR/PEG via coordination bonds to prepare a rod-like pH-responsive nanosystem (AuNR@FA-PR/PEG/CDDP) with chemotherapy/photothermal therapy. The rod-like morphology of AuNR@FA-PR/PEG was characterized by transmission electron microscope. In vitro drug release experiments showed the pH-responsive of AuNR@FA-PR/PEG/CDDP. In vivo real-time imaging assays proved AuNR@FA-PR/PEG/CDDP could rapidly enrich in the tumor area and stay for a long time because of folate targeting and their rod-like morphology. In vivo photothermal imaging assays showed AuNR@FA-PR/PEG/CDDP excellent photothermal performance, the average temperature of tumor region could reach 63.5 °C after 10 min irradiation. In vitro and in vivo experiments also demonstrated that the combined therapy of chemotherapy and photothermal therapy had an outstandingly synergistic effect and improved the therapeutic efficacy comparing with chemotherapy and photothermal therapy alone. Therefore, the prepared rod-like AuNR@FA-PR/PEG/CDDP will provide a new strategy for the effective treatment of cancer.

Precisely NIR-II-activated and pH-responsive cascade catalytic nanoreactor for controlled drug release and self-enhanced synergetic therapy.

Mesoporous polydopamine (MPDA) and MPDA-based nanosystems have been widely used in the field of photothermal therapy (PTT) and drug delivery. However, synthesis of the corresponding nanoplatforms for efficient PTT and controlled drug release simultaneously in the second near infrared (NIR-II) region remains a great challenge. Herein, a NIR-II and pH dual-responsive HMPDA@Cu2-xSe cascade catalytic nanoplatform was constructed by assembling hollow mesoporous polydopamine (HMPDA) with ultra-small Cu2-xSe, which could compensate the inadequate NIR-II-induced PTT effect of HMPDA and enhance the efficacy of chemodynamic therapy (CDT) simultaneously under NIR-II laser irradiation. Meanwhile, doxorubicin (DOX) and glucose oxidase (GOx) were encapsulated into the synthesized HMPDA@Cu2-xSe using the photothermal-induced phase change material (PCM) tetradecyl (1-TD) as a gatekeeper to achieve the controlled release of the cargo. Under 1064 nm laser, the generated heat could cause 1-TD melting, resulting in the release of large amounts of DOX and GOx. The released GOx could further catalyze glucose to H2O2 and gluconic acid, which in turn promoted the effects of PTT/CDT and the release of drugs. In vitro and in vivo experiments showed that the synthesized HMPDA@Cu2-xSe-DOX-GOx@PCM (HMPC-D/G@PCM) nanosystem exhibited a significant tumor cell inhibition effect by combining different treatment modes. Thus, this smart nanoplatform with multiple stimuli-activated cascade reactions provided a new idea for designing effective multi-modal combination therapy for tumors.

A multifunctional nanoamplifier with self-enhanced acidity and hypoxia relief for combined photothermal/photodynamic/starvation therapy.

Phototherapies, including photothermal therapy (PTT) and photodynamic therapy (PDT) have been potential noninvasive therapeutic modality with high efficiency, however, there still exist some intrinsic limitations that impede their clinical applications. Herein, taking the advantages of the synergistic effect and high reactivity of manganese dioxide (MnO2) nanosheets and glucose oxidase (GOx), multifunctional MPDA@MnO2-MB-GOx nanoamplifier was constructed for enhanced PTT, PDT, and starvation therapy. In tumor microenvironment (TME), MnO2 nanosheets on the surface of mesoporous polydopamine (MPDA) could react with endogenous hydrogen peroxide (H2O2) and generate oxygen (O2) to relieve tumor hypoxia, thus enhancing the efficacy of PDT and GOx catalysis. Glucose consumption under the catalysis of GOx will enhance the acidity of TME and increase intracellular H2O2 concentration, which in turn promotes the production of O2 by MnO2 nanosheets, thus forming efficient cascade reaction and maximizing the efficacy of the functional agents. Furthermore, the heat generated by MPDA under the irradiation of 808 nm laser can accelerate chemical reactions, thus further enhancing synergistic therapeutic efficacy. In vitro/vivo results emphasize that enhanced cancer cell death and tumor inhibition are gained by modulating unfavorable TME with the functional nanosystem, which highlights the promise of the synthesized MPDA@MnO2-MB-GOx nanomaterial to overcome the limitations of phototherapy.

Nitric Oxide and Cyclic Guanosine Monophosphate Signaling Mediates the Antidepressant Effects of Acupuncture in the Rat Model of Chronic Unpredictable Mild Stress.

BACKGROUND Depression is a major mood disorder. Some patients have been reported to improve following acupuncture. This study aimed to investigate the effects of acupuncture on behaviors associated with depression in the chronic unpredictable mild stress (CUMS) rat model. The expression of signaling pathway components of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) in the rat hippocampus and plasma were also measured. MATERIAL AND METHODS Male Sprague-Dawley rats (N=40) were divided into the control group (N=10), the model group (N=10), the acupuncture group (N=10), and the non-acupuncture group (N=10). The rat model was established by orphaning combined with chronic unpredictable mild stress (CUMS) for six weeks. The acupuncture group was given 21 days of treatment using acupoints (AP) or non-acupoints (NP). Rat behaviors associated with depression were tested using the sucrose preference test (SPT), the open field test (OFT), and the elevated plus maze (EPM) test. Enzyme-linked immunoassay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor subunits, NR1, NR2A, and NR2B in the rat plasma and hippocampus. RESULTS Acupuncture reversed the behaviors associated with depression in the CUMS rat model and reduced the expression of components of the NO and cGMP pathway in the rat hippocampus and plasma. CONCLUSIONS In the CUMS rat model, treatment with acupuncture reduced behaviors associated with depression, and these effects were associated with changes in the NO and cGMP signaling pathway.

Solanesol derived therapeutic carriers for anticancer drug delivery.

Metabolites of a large number of inert drug carriers can cause long-term exogenous biological toxicity. Therefore, carriers with simultaneous therapeutic effects may be a good choice for drug delivery. Herein, a series of pharmacologically active solanesol derivatives were synthesized and investigated for use as micellar drug carriers for cancer therapy. Solanesyl thiosalicylic acid (STS) was first synthesized by introducing a thiosalicylic acid group to solanesol, inspired by the characteristic structure of farnesyl thiosalicylic acid (FTS) which is a non-toxic inhibitor of all active forms of the RAS protein. Then, two amphiphilic derivatives of STS were formed with ester- and hydrazone (HZ)-bond linked methyl poly(ethylene glycol)(mPEG), mPEG-STS and mPEG-HZ-STS, respectively. The PEGylated STS could be formed stable nano-sized micelles loaded with Doxorubicin (DOX). In vitro, DOX loaded mPEG-STS and mPEG-HZ-STS micelles exhibited stronger tumor inhibition ability compared with free DOX. In vivo, blank mPEG-STS and mPEG-HZ-STS micelles showed an obvious inhibiting effect on tumor growth while the drug loaded micelles had the greatest tumor inhibition effect. The enhanced therapeutic effects and the synergistic effect observed with this solanesol-based drug delivery system could be attributed to the inherent therapeutic qualities of the drug carriers.