Effect of Banana (Musa sp.) Peels Extract in Nanoemulsion Dosage Forms for the Improvement of Memory: In Vitro & In Vivo Studies.

BACKGROUND: Banana (Musa sp.) is a plant rich in phytochemical compounds, especially antioxidants, which are hypothesized to inhibit the activity of acetylcholinesterase, an enzyme associated with Alzheimer's Disease. OBJECTIVE: This research aimed to study nanoemulsion preparations of Kepok banana (KEP-NE) and Tanduk banana (TAN-NE) peel extracts for their activities as antioxidants, acetylcholinesterase as well as tyrosinase inhibitors, and as agents to improve short-term memory. METHODS: Nanoemulsion was prepared using a combination of high shear homogenization and ultrasonication. The antioxidant activity test was carried out using DPPH and ABTS methods. Meanwhile, memory improvement was studied in a mouse model with memory impairment induced by alloxan (120 mg/kg b.w) using the Y-maze apparatus. ELISA performed determination of acetylcholinesterase and tyrosinase inhibition. RESULTS: Characterization of the nanoemulsion was performed to include particle size, antioxidant activity, acetylcholinesterase, and tyrosinase inhibition. The particle size and polydispersity index (PI) of KEP-NE and TAN-NE were 84.2 nm (PI: 0.280) and 94.1 nm (PI: 0.282), respectively. The antioxidant activity of DPPH showed that the respective IC50 values of KEP-NE and TAN-NE were 0.64 µg/mL and 1.97 µg/mL. At the same time, the values with the ABTS method were 1.10 µg/mL and 1.72 µg/mL, respectively. The IC50 of KEP-NE on acetylcholinesterase inhibition was 108.80 µg/mL, and that on tyrosinase inhibition was 251.47 µg/mL. The study of short-term memory in the Y-maze revealed that the groups Kepok peel extracts 100 and 300 mg/kg b.w and KEP-NE 100 and 300 mg/kg b.w significantly (P < 0.05) improved short-term memory. CONCLUSION: This study suggests that the nanoemulsion dosage form of Kepok banana peel extract has antioxidant and acetylcholinesterase inhibition and tyrosinase inhibition activities and could potentially be an adjunct alternative treatment for memory disorders. Modifying the smaller drug particle size contributes to the delivery system. The nanoemulsion can increase pharmacological activity.

Anti-Neuropathic Pain Activity of Ageratum conyzoides L due to the Essential Oil Components.

BACKGROUND: Neuropathic pain is one of the contributors to the global burdens of illness. At present many patients do not achieve satisfactory pain relief even with synthetic painkillers. Taking this into consideration, it is necessary to search for natural product-derived alternative treatment with confirmed safety and efficacy. Ageratum conyzoides L is a plant often used as an analgesic in Indonesia, however, anti-neuropathic pain activity of this plant is still unknown. OBJECTIVE: To determine the anti-neuropathic pain activity of the essential oil and non-essential oil component (distillation residue) of A. conyzoides L. METHODS: We conducted the separation of the essential oil component from other secondary metabolites through steam distillation. Both components were tested for anti-neuropathic pain activity using chronic constriction injury animal models with thermal hyperalgesia and allodynia tests. The animals were divided into 7 test groups, namely normal, sham, negative, positive (pregabalin at 0.195 mg/20 g BW of mice), essential oil component (100 mg/kg BW), and non-essential oil component (100 mg/kg BW). Naloxone was tested against the most potent anti-neuropathic pain component (essential oil or non-essential oil) to investigate the involvement of opioid receptors. RESULTS: The GC-MS of the essential oil component indicated the presence of 60 compounds. Meanwhile, non-essential oil components include alkaloid, flavonoid, polyphenol, quinone, steroid, and triterpenoid. This non-essential oil component contained a total flavonoid equivalent to 248.89 ppm quercetin. The anti-neuropathic pain activity test showed significantly higher activity of the essential oil component compared to the non-essential oil component and negative groups (p<0.05). Furthermore, the essential oil component showed equal activity to pregabalin (p>0.05). However, this activity was abolished by naloxone, indicating the involvement of the opioid receptor in the action of the essential oil component. CONCLUSION: The essential oil component of A. conyzoides L is a potential novel substance for use as anti-neuropathic pain.

Ameliorating Effects of Four-Week Fiber-Multivitamin Combination Treatment on Low-Density Lipoprotein Cholesterol, Total Cholesterol, and Apolipoprotein B Profiles in Hypercholesterolemic Participants.

Hyperlipidemia is one of the leading causes of death and requires lipid-lowering treatment to reduce morbidity and mortality. Effective and safe alternative and adjunctive therapies could be beneficial for patients with hyperlipidemia. To assess the effect of a fiber-multivitamin combination product on the lipid parameters low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), triglyceride (TG), and apolipoprotein B (Apo B) in patients with hypercholesterolemia, we conducted a double-blind, randomized, parallel-group study. Forty-one out of 50 randomized hypercholesterolemic participants recruited between August 2016 and March 2018 completed the trial. The participants were assigned to receive either test product (treatment group, n = 20) or placebo (placebo group, n = 21) for 4 weeks following a 6-week dietary intervention (based on education from a dietitian) run-in period. The primary outcome was LDL-c levels and the secondary outcomes were HDL-c, TC, TG, and Apo B levels. All of the outcomes were measured at baseline and week 4 after the completion of run-in period. Participants in both groups had similar LDL-c levels (142 ± 15.7 vs. 143 ± 19.3 mg/dL). After 4 weeks of exposure to test product, participants in the treatment group demonstrated a 17.25 ± 22.26 reduction in LDL-c (p < .05 vs. placebo). This improvement in LDL-c was accompanied by amelioration in TC and Apo B levels, without any detrimental effects on HDL and TG concentration. Results of the present study suggest that fiber-vitamin combination has potential to be used as an adjunct therapy for the management of hypercholesterolemia.

Local sustained delivery of bupivacaine HCl from a new castor oil-based nanoemulsion system.

Bupivacaine HCl (1-butyl-2',6'-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9 h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects. Herein, biodegradable oils were evaluated for use in nanoemulsions to enable sustained release kinetics of bupivacaine HCl. Only with castor oil, a clear and stable nanoemulsion was obtained without the occurrence of phase separation over a period of 3 months. High loading of bupivacaine HCl into the castor oil-based nanoemulsion system was achieved with about 98% entrapment efficiency and the resulting formulation showed high stability under stress conditions (accelerated stability test) regarding changes in visual appearance, drug content, and droplet size. We show herein that the in vitro release and in vivo pharmacokinetic profiles as well as pharmacodynamic outcome (pain relief test) after subcutaneous administration in rats correlate well and clearly demonstrate the prolonged release and extended duration of activity of our novel nanoformulation. In addition, the lower Cmax value achieved in the blood compartment suggests the possibility that the risk for systemic side effects is reduced. We conclude that castor oil-based nanomulsion represents an attractive pain treatment possibility to achieve prolonged local action of bupivacaine HCl.

Cardiovascular effects of Phaleria macrocarpa extracts combined with mainstay FAC regimen for breast cancer.

DLBS1425 is a bioactive compound extracted from Phaleria macrocarpa, with anti-proliferative, anti-inflammatory and anti-angiogenic properties against cancer cells. The present study was aimed to assess cardiotoxicity of DLBS1425, compared to the mainstay regimen for breast cancer, 5-fluorouracil:doxorubicin:cyclophosphamide (FAC, given at 500/50/500 mg/m(2)). Treatment with FAC regimen at standard dose resulted in very severe toxicity, so mice had no chance to survive for more than 7 days following initial drug treatment. Furthermore, histological examination on the heart revealed severe muscular damage when mice were given the FAC regimen alone (severe toxicity). FAC as chemotherapeutic regimen exerted high toxicity profile to the cardiovascular cells in this experiment. Meanwhile, treatment with DLBS1425 alone up to a dose equivalent to as high as 300 mg three times daily in human had no hazardous consequences on the heart, hematological feature, as well as general safety. In the cardiovascular cells, DLBS1425 in the presence of FAC regimen (one-eight of the initial dose) gave protection to the cardiac muscle cells as well as other hematological features. Taken together, results of the present study suggest that DLBS1425 is safe when used as adjuvant therapy for breast cancer and may be even protective against cardiac cellular damage produced by chemotherapeutic regimen.