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Andrographolide has been shown to have a pharmacological effect as an antidiabetic. Nevertheless, the comprehensive mechanism of action has yet to be determined. Andrographolide is a primary component of the sambiloto herb (Andrographis paniculata (Burm.f.) Nees), in which a simple isolation process can obtain high yields. This study aimed to explain the anti‐diabetic effect of andrographolide compared to pioglitazone (a positive control) on glucose uptake by measuring the expression levels of peroxisome proliferator‐activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT‐4) genes in 3T3‐LI mouse adipocytes as an in vitro model. The differentiation of mature adipocytes from 3T3‐L1 fibroblasts was induced with 3‐isobutyl‐1‐methylxanthine, dexamethasone, and insulin. Andrographolide was provided through direct isolation from A. paniculata herbs. The gene expression was detected using the reverse transcription‐polymerase chain reaction (RT‐PCR). Pioglitazone and andrographolide significantly increased glucose uptake capability. Andrographolide was able to increase the mRNA levels of PPARγ and GLUT‐4 compared to pioglitazone with the best concentration at 5.6 µM. In conclusion, andrographolide can improve glucose uptake by increasing mRNA levels of PPARγ and GLUT‐4 that encodes protein, which are key factors for glucose homeostasis. Therefore, this finding further establishes the potency of andrographolide from A. paniculata as an antidiabetic.

Background: Hyperinsulinemia, a common feature in PCOS, have been found to contribute to metabolic disturbance, such as dyslipidaemia and diabetes mellitus type 2. Oral anti-diabetic medications have been prescribed to alleviate this effect. We sought to fnd whether DLBS3233, an insulin sensitizer, could alleviate dyslipidaemia in women with PCOS with high BMI. Aim: This study aimed to investigate the effect of DLBS3233, an herbal combination of C burmanii and L spesiosa extract, on lipid profle, insulin resistance, and free testosterone of women with PCOS with high BMI. Study Setting and Design: This was a controlled trial conducted in Dr. Cipto Mangunkusumo Hospital, Jakarta, and Dr Hasan Sadikin Hospital, Bandung, Indonesia.Materials and Methods: A controlled trial was conducted on 62 volunteers diagnosed with PCOS according to Rotterdam criteria and exhibited insulin resistance as signifed by HOMA-IR > 2.0; baseline lipid profile (LDL, HDL, Triglyceride and Total cholesterol) and free testosterone concentration were obtained. Participants were given 100 mg of DLBS3233 in the morning, and volunteers were followed up monthly, with laboratory tests conducted at the third and sixth months. Data were analysed through intention-to-treat analysis, separating high BMI (≥25 kg/m2) subjects. Statistical Analysis: Repeated-measures model. Results: DLBS3233 improved lipid profle and insulin sensitivity by reducing triglycerides, HOMA-IR, and free testosterone in subjects with high BMI. Limitations and Implications: The current study does not compare the effect of DLBS3233 with a control group. A larger study with a proper control group would have to be conducted to have more conclusive results. Conclusion: This study showed that DLBS3233 holds promise as a novel therapy to improve lipid profle for women with PCOS.

The main bitter constituents of sambiloto (Androgaphis paniculata (Burm., F) Ness) are diterpene lactones, namely andrographolide and deoxyandrographolide which have been reported to have antidiabetic, cytotoxic, antiatherosclerosis, anti-inflammatory, and antimicrobial activity. There are many studies that performed the isolation of deoxyandrographolide and andrographolide from A. paniculata herbs, but most of them included several steps that make them not efficient. This research was conducted to do an isolation of deoxyandrographolide and andrographolide through liquid-liquid fractionation (LLF) due to its simplicity, low cost, and time efficient. The extraction of deoxyandrographolide and andrographolide from the herbs was carried out using chloroform as the solvent by using Soxhlet apparatus, and LLF was performed to isolate the compounds. The identities of the compounds were confirmed by TLC scanner compared to its standard references. Hence, these present methods were successfully isolated and determined deoxyandrographolide and andrographolide of A. paniculata. The compounds were also showed relatively moderate cytotoxicity on 3T3-L1 cell lines using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, with LC50 of deoxyandrographolide and andrographolide; 29.3173 µg/mL and 37.7011 µg/mL, respectively.

Neuropathic pain affects 7% to 10% of the population and has major effects on quality of life. It is defined as pain caused by a lesion or disease of the somatosensory nervous system and may be central or peripheral. Diagnostic testing may yield inconclusive or inconsistent results, so physicians often rely on clinical judgment based on the history and physical examination findings. Questionnaires and scoring systems can aid in diagnosis. Neuropathic pain is differentiated from other types of chronic pain by abnormal sensory symptoms, such as shooting pain, burning pain, or numbness. It is difficult to manage and can be accompanied by mood and sleep disturbances. Referral for psychotherapy may be useful for these patients. Nonpharmacotherapy options include mindfulness training, transcutaneous electrical nerve stimulation, and massage. Acupuncture also may be effective, but the data are mixed. Topical drugs (eg, lidocaine, capsaicin), gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are considered first-line drugs. Tramadol is considered a second-line drug, but may considered first-line for certain patients. For persistent pain, physicians can consider referring patients to a pain specialist for nerve blocks or other procedural interventions. Opioids may be considered for refractory pain, but their additional benefit has been shown to be modest compared with those of other treatments.

Asthma affects more than 25 million people in the United States, and 62% of adults with asthma do not have adequately controlled symptoms. Asthma severity and level of control should be assessed at diagnosis and evaluated at subsequent visits using validated tools such as the Asthma Control Test or the asthma APGAR (activities, persistent, triggers, asthma medications, response to therapy) tools. Short-acting beta2 agonists are preferred asthma reliever medications. Controller medications consist of inhaled corticosteroids, long-acting beta2 agonists, long-acting muscarinic antagonists, and leukotriene receptor antagonists. Treatment typically begins with inhaled corticosteroids, and additional medications or dosage increases should be added in a stepwise fashion according to guideline-directed therapy recommendations from the National Asthma Education and Prevention Program or the Global Initiative for Asthma when symptoms are inadequately controlled. Single maintenance and reliever therapy combines an inhaled corticosteroid and long-acting beta2 agonist for controller and reliever treatments. This therapy is preferred for adults and adolescents because of its effectiveness in reducing severe exacerbations. Subcutaneous immunotherapy may be considered for those five years and older with mild to moderate allergic asthma; however, sublingual immunotherapy is not recommended. Patients with severe uncontrolled asthma despite appropriate treatment should be reassessed and considered for specialty referral. Biologic agents may be considered for patients with severe allergic and eosinophilic asthma.

Depression affects an estimated 8% of persons in the United States and accounts for more than $210 billion in health care costs annually. The U.S. Preventive Services Task Force (USPSTF) and American Academy of Family Physicians recommend screening for depression in the general adult population. Additionally, the USPSTF recommends screening children and adolescents 12 to 18 years of age for major depressive disorder. All screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. The two-item and nine-item Patient Health Questionnaires (PHQs) are commonly used validated screening tools. The PHQ-2 has sensitivity comparable with the PHQ-9 in most populations; however, the specificity of the PHQ-9 ranges from 91% to 94%, compared with 78% to 92% for the PHQ-2. If the PHQ-2 is positive for depression, the PHQ-9 or a clinical interview should be administered. Screening all postpartum women for depression is recommended by the USPSTF, American Academy of Family Physicians, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. Women should be screened for depression at least once during the perinatal period using the PHQ-2, PHQ-9, or Edinburgh Postnatal Depression Scale. In older adults, the Geriatric Depression Scale is also an appropriate screening tool for depression. If screening is positive for possible depression, the diagnosis should be confirmed using Diagnostic and Statistical Manual of Mental Disorders, 5th ed., criteria.

This article reviews recent medical literature to provide an overview of the recognition and treatment of the two broad categories of cold injuries, freezing and nonfreezing. Frostbite, a freezing cold injury, is treated traditionally with rapid rewarming followed by tissue care and surgical debridement of necrotic tissue. Recently, newer therapies aimed at prevention of tissue necrosis have shown improved outcomes compared with more traditional therapies. These newer treatment regimens for frostbite include the use of various drugs such as ibuprofen, aspirin, warfarin, tissue plasminogen activator, and prostacyclin. The use of Tc bone scans, magnetic resonance imaging arthrogram, or angiography may have prognostic value for early determination of the extent of tissue loss. The more common nonfreezing cold injuries, though less severe than frostbite, may lead to short- and long-term complications requiring treatment and are discussed also.

We have previously reported the chemistry and antinociceptive properties of a series of glycosylated enkephalin analogs (glycopeptides) exhibiting approximately equal affinity and efficacy at δ opioid receptors (DORs) and μ opioid receptors (MORs). More detailed pharmacology of the lead glycopeptide MMP-2200 [H₂N-Tyr-D-Thr-Gly-Phe-Leu-Ser-(O-β-D-lactose)-CONH₂] is presented. MMP-2200 produced dose-related antinociception in the 55°C tail-flick assay after various routes of administration. The antinociceptive effects of MMP-2200 were blocked by pretreatment with the general opioid antagonist naloxone and partially blocked by the MOR-selective antagonist β-funaltrexamine and the DOR-selective antagonist naltrindole. The κ opioid receptor antagonist nor-binaltorphimine and the peripherally active opioid antagonist naloxone-methiodide were ineffective in blocking the antinociceptive effects of MMP-2200. At equi-antinociceptive doses, MMP-2200 produced significantly less stimulation of locomotor activity compared with morphine. Repeated administration of equivalent doses of morphine and MMP-2200 (twice daily for 3 days) produced antinociceptive tolerance (~13- and 5-fold rightward shifts, respectively). In acute and chronic physical dependence assays, naloxone precipitated a more severe withdrawal in mice receiving morphine compared with equivalent doses of the glycopeptide. Both morphine and MMP-2200 inhibited respiration and gastrointestinal transit. In summary, MMP-2200 acts as a mixed DOR/MOR agonist in vivo, which may in part account for its high antinociceptive potency after systemic administration, as well as its decreased propensity to produce locomotor stimulation, tolerance, and physical dependence in mice, compared with the MOR-selective agonist morphine. For other measures (e.g., gastrointestinal transit and respiration), the significant MOR component may not allow differentiation from morphine.

Aims: The current studies were designed to compare the in vivo potencies of the opioid antagonists 6beta-naltrexol and naltrexone in blocking the effects of the opioid agonist hydrocodone following intravenous (i.v.) or oral (p.o.) administration., Main Methods: Adult male CD-1 mice were used for all experiments. The 55 degrees C tail-flick assay was used to assess the CNS antinociceptive activity of hydrocodone, and a charcoal meal gastrointestinal transit assay was used to assess the peripheral effects of hydrocodone. Graded antagonist dose-response curves for i.v. and p.o. 6beta-naltrexol and naltrexone were generated to determine ID(50) antagonist potency estimates against fixed doses of hydrocodone., Key Findings: Both antagonists produced dose-related blockade of hydrocodone-induced antinociception and inhibition of gastrointestinal transit. Naltrexone was between 5- and 13-fold more potent than 6beta-naltrexol in blocking a CNS effect of hydrocodone, whereas the drugs were nearly equipotent in blocking inhibition of gastrointestinal transit. Co-administration studies indicated an approximate 10-fold greater potency of 6beta-naltrexol for antagonism of hydrocodone-induced inhibition of gastrointestinal transit versus antinociception, whereas naltrexone blocked both effects with near equal potency. 6beta-naltrexol produced a longer duration of antagonist blockade and had a slower time to peak effect compared to naltrexone., Significance: The pharmacology of 6beta-naltrexol differentiates it from currently available opioid antagonists. This includes an intermediate selectivity for peripheral versus central opioid receptors, a long duration of action, and neutral antagonist qualities in opioid exposed systems. These properties render it a drug candidate for a co-formulation product with opioid analgesics to reduce peripheral opioid side effects and limit abuse potential.

Enantiomeric N-phenethyl-m-hydroxyphenylmorphans with various substituents in the ortho, meta or para positions of the aromatic ring in the phenethylamine side-chain (chloro, hydroxy, methoxy, nitro, methyl), as well as a pyridylethyl and a indolylethyl moiety on the nitrogen atom, were synthesized and their binding affinity to the mu-, delta-, and kappa-opioid receptors was examined. The higher affinity ligands were further examined in the [(35)S]GTPgammaS assay to study their function and efficacy. 3-((1R,5S)-(-)-2-(4-Nitrophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) was found to be a mu-agonist and delta-antagonist in that functional assay and was about 50 fold more potent than morphine in vivo. 3-((1R,5S)-(-)-2-(4-Chlorophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) and several other ligands displayed inverse agonist activity at the delta-opioid receptor. The absolute configuration of all of the reported compounds was established by chemical conversion of (-)- to 1R,5S-(-)-.HBr.