In Octodon degus, the aging process is not equivalent between sexes and worsens for females. To determine the beginning of detrimental features in females and the ways in which to improve them, we compared adult females (36 months old) and aged females (72 months old) treated with Andrographolide (ANDRO), the primary ingredient in Andrographis paniculata. Our behavioral data demonstrated that age does not affect recognition memory and preference for novel experiences, but ANDRO increases these at both ages. Sociability was also not affected by age; however, social recognition and long-term memory were lower in the aged females than adults but were restored with ANDRO. The synaptic physiology data from brain slices showed that adults have more basal synaptic efficiency than aged degus; however, ANDRO reduced basal activity in adults, while it increased long-term potentiation (LTP). Instead, ANDRO increased the basal synaptic activity and LTP in aged females. Age-dependent changes were also observed in synaptic proteins, where aged females have higher synaptotagmin (SYT) and lower postsynaptic density protein-95 (PSD95) levels than adults. ANDRO increased the N-methyl D-aspartate receptor subtype 2B (NR2B) at both ages and the PSD95 and Homer1 only in the aged. Thus, females exposed to long-term ANDRO administration show improved complex behaviors related to age-detrimental effects, modulating mechanisms of synaptic transmission, and proteins.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to intrinsic or acquired resistance to chemotherapy, such as Gemcitabine (Gem). Naturally occurring botanicals, including Andrographis (Andro), can help enhance the anti-tumorigenic therapeutic efficacy of conventional chemotherapy through time-tested safety and cost-effectiveness. Accordingly, we hypothesized that Andro might reverse Gem resistance in PDAC. The critical regulatory pathways associated with Gem resistance in PDAC were identified by analyzing publicly available transcriptomic profiling and PDAC tissue specimens. A series of systematic in vitro experiments were performed using Gem-resistant (Gem-R) PDAC cells and patient-derived 3D-organoids to evaluate the Andro-mediated reversal of Gem resistance in PDAC. Transcriptomic profiling identified the calcium signaling pathway as a critical regulator of Gem-resistance (Fold enrichment: 2.8, p = 0.002). Within this pathway, high ERBB3 expression was significantly associated with poor prognosis in PDAC patients. The combination of Andro and Gem exhibited superior anti-cancer potential in Gem-R PDAC cells through potentiating cellular apoptosis. The combined treatment down-regulated ERBB3 and decreased intracellular calcium concentration in Gem-R PDAC cells. Finally, these findings were successfully interrogated in patient-derived 3D-organoids. In conclusion, we demonstrate novel evidence for Andro-mediated reversal of chemoresistance to Gem in PDAC cells through the regulation of ERBB3 and calcium signaling.

Andrographolide (Andro), the major constituent of Andrographis paniculata Nees (Acanthaceae), is was known to reduces inflammatory reaction. In the current study, the ability of Andro to reduce pain sensation in a rat post-operative wound model was explored. The hind paws of 18 Sprague-Dawley rats (SD) bearing post-operative wounds received the following three treatments: Saline, Andro via direct injection into the paw (Andro-injected) and Tablet containing Andro + poly (lactic-co-glycolic acid) (PLGA) (Andro-tablet). Von Frey tests assessed mechanical allodynia at 1, 3, 5 h and 1-, 2-, 3-, 4-, and 5-days post-operation. Behavioral analyses were performed to measure reaction threshold and reaction frequencies. Immunoreactivity of p-ERK and GluR1 was examined in the dorsal horn of the spinal cord. Histopathological and immunostaining studies were conducted on paw epidermis to observe the gross morphology and angiogenesis. The threshold for inducing allodynia increased and the reaction frequency reduced in the Andro-injected group compared to the saline-group, at 3 h post-surgery and the effect lasted between 3-4 days. The threshold for inducing pain and reaction frequency for the Andro-tablet group did not differ from the saline-treated group. The levels of p-ERK and GluR1 in the dorsal horn were reduced after Andro treatment. No significant difference in wound healing index was observed between saline and Andro-injected groups, but CD-31 staining showed less angiogenesis in the Andro-injected group. Andro significantly reduced mechanical allodynia compared to saline treatment, both in shorter and longer time frames. Furthermore, Andro influenced the expression of p-ERK and GluR1 in the dorsal horn, and the angiogenesis process in the wound healing area.

Steroid analysis in clinical laboratories is dominated by immunoassays (IAs) that have a high sample turnover but are inherently limited in trueness, precision, and sensitivity. Liquid chromatography coupled to mass spectrometry (LC-MS/MS) has proved to be a far more capable tool, delivering better sensitivity, specificity, and the possibility of parallel analysis of multiple steroids and metabolites, providing the endocrinologist with more reliable and comprehensive diagnostic information. An LC-MS/MS assay with gradient elution over less than eight minutes and a one-step sample preparation combining protein precipitation with phospholipid removal of off-line solid-phase extraction was developed and validated. It allowed the quantification of 11-deoxycorticosterone (11-DOC), 11-deoxycortisol (11-DF), 17-OH-progesterone (17P), 21-deoxycortisol (21-DF), androstenedione (ANDRO), aldosterone (ALDO), corticosterone (CC), cortisol (CL), cortisone (CN), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), estradiol (E2), progesterone (PROG), and testosterone (TES) in human serum. Interday imprecision was generally better than 15%, trueness was proven by recovery experiments with ISO 17034-certified reference materials, proficiency testing (UK NEQAS), and measuring serum reference standards. In-house comparison against IVD-CE-certified immunoassays (IA) for 17P, ANDRO, CL, DHEAS, E2, PROG, and TES was conducted by assessing leftover routine patient samples and purpose-built patient serum pools. None of the compared routine IAs were meeting the standards of the LC-MS/MS. Insufficient overall comparability was found for ANDRO and 17P (mean bias > +65%). Accuracy limitations at lower concentrations were present in IAs for PROG, E2, and TES.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is selectively lethal to cancer cells and harmless to normal cells, making it a potential agent for cancer therapy. However, some breast cancer cells are resistant to TRAIL. This study revealed that andrographolide (Andro), an extract from Andrographis paniculate, a natural compound, sensitized breast cancer cells to TRAIL-induced tumor suppression; it identified apoptosis-associated protein regulation, reactive oxygen species accumulation, mitochondria membrane potential disruption, caspase cascade activation, and gasdermin-E cleavage to be involved in the tumor lethality mediated by Andro combined with TRAIL treatment. The flow cytometry results showed the combination of Andro and TRAIL repressed breast cancer cells by cell death induction, and the assessment of combined index indicated that the combined treatment with Andro and TRAIL repressed breast cancer cells synergistically. Blotting results displayed Andro and TRAIL combination elevated TRAIL-associated receptors, death receptors 4 and 5, at protein levels. These results provided critical insight into breast cancer patients' therapy and exploration direction for TRAIL clinical application.

Background: Spinal cord injury (SCI) is a common disorder of the central nervous system with considerable socio-economic burden. Andrographolide (Andro), the main active component of Andrographis paniculata, has exhibited neuroprotective effects in different models of neurological diseases. The aim of this study was to evaluate the neuroprotective effects of Andro against SCI and explore the related mechanisms. Methods: SCI was induced in rats by the Allen method, and the modeled animals were randomly divided into sham-operated, SCI, SCI + normal saline (NS) and SCI + Andro groups. The rats were injected intraperitoneally with Andro (1 mg/kg) or the same volume of NS starting day one after the establishment of the SCI model for 28 consecutive days. Post-SCI tissue repair and functional recovery were evaluated by measuring the spinal cord water content, footprint tests, Basso-Beattie-Bresnahan (BBB) scores, hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis, oxidative stress and inflammation, as well as axonal regeneration and remyelination were analyzed using suitable markers. The in vitro model of SCI was established by treating cortical neurons with H2O2. The effects of Andro on apoptosis, oxidative stress and inflammation were evaluated as indicated. Results: Andro treatment significantly improved tissue repair and functional recovery after SCI by reducing apoptosis, oxidative stress and inflammation through the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf-2/HO-1) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, Andro treatment promoted M2 polarization of the microglial cells and contributed to axonal regeneration and remyelination to improve functional recovery after SCI. In addition, Andro also attenuated apoptosis, oxidative stress and inflammation in H2O2-stimulated cortical neurons in vitro. Conclusion: Andro treatment alleviated SCI by reducing apoptosis, oxidative stress and inflammation in the injured tissues and cortical neurons, and promoted axonal regeneration and remyelination for functional recovery.

1. This study aimed to study the preventive and therapeutic effects of andrographolide (Andro) during Mycoplasma gallisepticum HS strain (MG) infection in ArborAcres (AA) broilers.2. The minimum inhibitory concentration (MIC) of Andro against MG was measured. Broiler body weight, feed efficiency, morbidity, cure rate and mortality were recorded during the experiment. Air sac lesion scores and immune organ index were calculated. Expression of pMGA1.2 in lung tissue and serum biochemical indices were examined. Histopathological examinations of immune organs, liver, trachea and lung tissue were conducted by Haematoxylin and Eosin stain.3. MIC was 3.75 μg/mL and Andro significantly inhibited the expression of pMGA1.2 (P ≤ 0.05). Compared with control MG-infected group, Andro low-dose and high-dose prevention reduced the morbidity of chronic respiratory disease in 40.00% and 50.00%, respectively. Mortality of C, D and E group was 16.67%, 10.00% and 6.67%, respectively. Cure rate of E, F, G and H group was 92.00%, 92.86%, 93.33% and 100.0%, respectively. Compared with control MG-infected group, Andro treatment significantly increased average weight gain (AWG), relative weight gain rate (RWG) and feed conversion rate (FCR) at 18 to 24 days (P ≤ 0.05). Compared with control group, Andro alone treatment significantly increased AWG in broilers (P ≤ 0.05).4. Compared with control MG-infected group, Andro significantly attenuated MG-induced air sac lesion, immune organs, liver, trachea and lung damage in broilers. Andro alone treatment did not induce abnormal morphological changes in these organs in healthy broilers. Serum biochemical analysis results showed, comparing with control MG-infected group, Andro significantly decreased the content of total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, urea, creatinine, uric acid, total cholesterol, and increased the albumin/globulin ratio and content of alkaline phosphatase, apolipoprotein B and apolipoprotein A-I in a dose-dependent manner (P ≤ 0.05).5. Andro could act as a potential agent against MG infection in broilers.

Ankle sprains (AS) are common in the military population, with a prevalence 5 to 8 times higher than that for civilians. The aim of this study was to evaluate in patients with severe AS the impact of disuse on thigh muscle induced by unloading and immobilization due to care. This study focused on muscle trophicity and dynamometric strength. In this observational prospective study, assessments were repeated at 3 visits: close to injury, 15 and 30 days following the sprain. The injured limb was compared to the contralateral limb. A dynamometer assessment was used to monitor changes in strength and fatigue of the thigh muscles of both limbs. Isometric and isokinetic concentric evaluation of peak torque (PTiso and PTdyn), total work (Wt), and peak torque time integral (IPT) of thigh muscles. Full follow-up was obtained in 30 subjects. The injured limbs showed significant deficits in the mean (SD). The quadriceps PTiso and IPT deficits were -12.6% ± 1.9% (P < .0001) and -13.27% ± 1.8% (P < .0001), respectively. The quadriceps PTdyn showed a significant deficit since V2 (-12.2.5% ± 2.0). The quadriceps Wt presented a significant deficit of -4.2% ± 2.4 (P < .0007) at 1 month. The hamstring PTdyn deficit presented a mean loss of -16.5% ± 2.4% (P < .0001). The hamstring Wt deficit was -13.7% ± 2.3% (P < .001). The analysis of variance showed that the grade of the sprain had a significant effect on the quadriceps PTq deficit (P < .016) but not the type of discharge. Our study showed that disuse leads to a significant deficit in the strength of knee muscles within 1 month. It is noteworthy that the hamstrings are more affected than the quadriceps. The rehabilitation protocol to prevent the risk of iterative ankle injuries and secondary knee injuries should incorporate early training of both quadriceps and hamstrings.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Alzheimer's disease (AD) is a neurodegenerative disorder clinically manifested by a gradual cognitive decline. Intracerebroventricular injection (ICV) of streptozotocin (STZ), a model of sporadic AD (sAD), shows many aspects of sAD abnormalities (i.e., neuroinflammation, oxidative stress, protein aggregation), resulting in memory impairment. Andrographolide (ANDRO), a natural diterpene lactone, has numerous bioactivities including anti-inflammatory and antioxidant properties. Studies in rodents revealed that ANDRO has neuroprotective properties and restores cognitive impairment. In the present study, we investigated the effects of ANDRO in the ICV-STZ model relative to short-term spatial memory (object location test (OLT) and Y maze test), short-term recognition memory (object recognition test (ORT)), locomotor activity (open field test (OFT)), expression of amyloid precursor protein (APP), and activation of astrocytes (glial fibrillary acidic protein (GFAP) expression) and microglia (ionized calcium-binding adapter molecule-1 (Iba-1) immunohistochemistry) in the prefrontal cortex (PFC) and hippocampus (HIP). Wistar rats were injected ICV with STZ (3 mg/kg) or vehicle and treated with ANDRO (2 mg/kg, i.p.; three times per week). After four weeks, ANDRO attenuated the impairments of the Y maze and ORT performances, and the increase of astrocyte activation in the PFC induced by the ICV-STZ model. In addition, ANDRO decreased the number of activated microglia cells in the HIP of STZ-injected rats. The APP expression was not altered, neither by the STZ nor ANDRO. ANDRO showed a beneficial effect on memory impairment and neuroinflammation in the STZ model of AD.

Lymphatic filariasis caused by filarial nematode is an important disease leading to considerable morbidity throughout tropical countries. Even after specific elimination programs, the disease continue to spread in endemic countries. Thus newer therapeutic interventions are urgently needed to control the spread. In the present study, we have seen the effect of andrographolide (andro), a diterpenoid lactone from the leaves of Andrographis paniculata on filarial parasite Setaria cervi. There was time and concentration dependent decrease in motility and viability leading to death of parasite after 6 h of the exposure of andro. Andro showed potential antifilarial activity with an IC50 value of 24.80 μM assessed through MTT assay. There was concentration dependent decrease in the antioxidant enzymes activity and increase in proapoptotic markers after 5 h exposure of andro. Further, molecular docking analysis revealed that andro binds with filarial glutathione-S-transferase at glutathione (GSH) binding site and inhibiting enzyme activity competitively. Andro induced oxidative stress mediated apoptosis in parasites as evidenced by increase in the intracellular reactive oxygen species (ROS) and apoptotic markers.Therefore this study suggested that andro could be further explored as a new antifilarial drug.

Background: Andrographolide (Andro) is a diterpenoid component of the plant Andrographis paniculata that is known for its anti-tumor activity against a variety of cancer cells. Methods: We studied the effects of Andro on the viability of the human leukemia monocytic cell line THP-1 and the human multiple myeloma cell line H929. Andro was compared with cytosine arabinoside (Ara-C) and vincristine (VCR), which are well-established therapeutics against hematopoietic tumors. The importance of reactive oxygen species (ROS) production for the toxicity of each agent was investigated by using an inhibitor of ROS production, N-acetyl-L-cysteine (NAC). Results: Andro reduced the viability of THP-1 and H929 in a concentration-dependent manner. H929 viability was highly susceptible to Andro, although only slightly susceptible to Ara-C. The agents Andro, Ara-C, and VCR each induced apoptosis, as shown by cellular shrinkage, DNA fragmentation, and increases in annexin V-binding, caspase-3/7 activity, ROS production, and mitochondrial membrane depolarization. Whereas Ara-C and VCR increased the percentages of cells in the G0/G1 and G2/M phases, respectively, Andro showed little or no detectable effect on cell cycle progression. The apoptotic activities of Andro were largely suppressed by NAC, an inhibitor of ROS production, whereas NAC hardly affected the apoptotic activities of Ara-C and VCR. Conclusions: Andro induces ROS-dependent apoptosis in monocytic leukemia THP-1 and multiple myeloma H929 cells, underlining its potential as a therapeutic agent for treating hematopoietic tumors. The high toxicity for H929 cells, by a mechanism that is different from that of Ara-C and VCR, is encouraging for further studies on the use of Andro against multiple myeloma.

Andrographolide (andro) and its derivatives have been reported to have antitumor activity by arresting the cell cycle. However, the more precise mechanism has been controversial. Here, a proteome chip was used to screen drug targets in cells, and we discovered that andro can bind to PDCD2 (PD2), which has been shown to be associated with the cell cycle and mRNA nuclear export. Then, RNA-binding protein immunoprecipitation for PD2 was used to detect the quantity of cell cycle-related mRNAs, and the nuclear distribution difference analyses of these mRNAs in tumor cells after andro intervention, followed by systematic experiments, were performed to assess the downstream effects of this event in vivo and in vitro. Thus, the target spectrum of andro was revealed at the level of the human proteome chip for the first time, and this work demonstrated that andro, through targeting PD2, blocks the nuclear output of CDK mRNAs in the nucleus of tumor cells, further reduces the expression of cell CDK proteins, and finally causes tumor cell cycle arrest in phenotype and tumor tissue growth arrest in vivo.

Ulcerative colitis (UC), an inflammatory disease, is widely thought to be associated with colonic barrier damage and inflammatory response. With the destruction of the colonic barrier, lipopolysaccharide (LPS) enters the liver through the portal vein and causes liver injury. Liver injury in turn exacerbates UC to form a vicious cycle, so the treatment of liver injury cannot be ignored. Andrographolide (Andro) has a protective effect against colitis and liver injury, but with low bioavailability. Andrographolide sodium bisulfite (ASB), a water-soluble sulfonate of Andro, has better bioavailability, whether it has a better curative effect against UC and liver injury is rarely reported. Hence, we investigated the protective effect and potential mechanism of ASB against dextran sulfate sodium (DSS)-induced UC and liver injury in mice. The results showed that treatment with ASB significantly relieved the clinical symptoms of UC and liver injury by reducing disease activity index, inhibiting gut-derived LPS leakage, and improving colonic and hepatic injury, and its curative effect was better than Andro. Moreover, ASB effectively decreased the YAP-mediated colonic inflammation and TLR4/MyD88/NF-κB-mediated pro-inflammatory factor release in the liver. Both colonic and hepatic inflammation were associated with macrophage proinflammatory polarization, but they were significantly inhibited by ASB. ASB showed good safety in the treatment of UC and liver injury and has no nephrotoxicity as previously described. In conclusion, ASB has an effective protective effect on DSS-induced UC and liver injury, mainly by suppressing macrophage proinflammatory polarization from the gut-liver axis.

Burkholderia pseudomallei (B. pseudomallei) is a Gram-negative pathogen that causes melioidosis, a deadly but neglected tropical disease. B. pseudomallei is intrinsically resistant to a growing list of antibiotics, and alternative antimicrobial agents are being sought with urgency. In this study, we synthesize andrographolide-stabilized silver nanoparticles (andro-AgNPs, spherically shaped with 16 nm average diameter) that show excellent antimicrobial activity against B. pseudomallei, including ceftazidime-resistant strains, being 1-3 orders of magnitude more effective than ceftazidime and 1-2 orders of magnitude more effective than other green-synthesized AgNPs. The andro-AgNPs are meanwhile non-toxic to mammalian cell lines. The mode of action of Andro-AgNPs toward B. pseudomallei is unraveled by killing kinetics, membrane neutralization, silver ions (Ag+) release, reactive oxygen species (ROS) induction, membrane integrity, and cell morphology change studies. The antimicrobial activity and mode of action of andro-AgNPs against B. pseudomallei reported here may pave the way to alternative treatments for melioidosis.

The COVID-19 outbreak is likely to affect both the occurrence and the reporting of abuse or neglect in vulnerable adults in a variety of ways. This study aims to explore such effects based on the alerts reported to the national system dedicated to these situations by the Ministry of Solidarity and Health in France.

Limited data indicate that a low-dose (100 mg) subcutaneous testosterone pellet given to a nursing mother appears not to increase milk testosterone levels markedly. Subcutaneous testosterone cypionate does increase milk testosterone levels. However, testosterone has low oral bioavailability because of extensive first-pass metabolism, so it appears to not increase serum testosterone levels in breastfed infants. Breastfed infants appear not to be adversely affected by maternal or transgender paternal testosterone therapy. High doses of testosterone can suppress lactation.

Mycoplasma gallisepticum (MG) is the primary etiologic agent of chronic respiratory disease (CRD) in chickens. Respiratory tract inflammation and apoptosis are the main features of CRD. Andrographolide (Andro), a natural small molecule compound, is known for its excellent anti-pathogenic and anti-inflammatory properties. Hence, this study was to evaluate the anti-inflammation and anti-apoptosis effects of Andro as well as the underlying mechanism in the chicken lungs and primary alveolar type II epithelial cells (AEC II). Results showed Andro had no side effects on AEC II viability at concentrations below 200 μg/ml. Compared with the model group, terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL), western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays (ELISA) results showed Andro treatment significantly reduced apoptosis in the chicken lungs and AEC II, and down-regulated the expression levels of the protein of MG adhesin 1.2 (pMGA1.2), IL-1β, TNF-α, IL-6, Bax, Caspase 9 and Caspase 3, and up-regulated the expression levels of Bcl-2 and Bcl-xL in the chicken lungs, serum and AEC II (P ≤ 0.05). Moreover, Andro inhibited the MG-induced JAK/PI3K/AKT signal pathway activation in the chicken lungs and AEC II. Inhibiting of the JAK/PI3K/AKT signal pathway significantly alleviated MG-induced inflammation and apoptosis in the AEC II. Andro may exert an anti-inflammatory and anti-apoptotic effect by inhibiting the JAK/PI3K/AKT signal pathway in the chicken lungs and AEC II. In conclusion, Andro could act as a potential agent against MG infection by inhibiting the JAK/PI3K/AKT signal pathway and pMGA1.2 expression in the chickens.

Tuberculosis (TB) remains a leading threat to public health worldwide with Mycobacterium tuberculosis (Mtb) infections causing long-term abnormal and excessive inflammatory responses, which in turn lead to lung damage and fibrosis, and ultimately death. Host-directed therapy (HDT) has been shown to be an effective anti-TB strategy in the absence of effective anti-TB drugs. Here, we used an in vitro macrophage model of Mtb infection to evaluate the effects of andrographolide (Andro), extracted from Andrographis paniculata, on pyroptosis in Mtb-infected macrophages. We evaluated the molecular mechanisms underlying these outcomes. These evaluations revealed that Andro downregulated the expression of proinflammatory miR-155-5p, which then promoted the expression of Nrf2 to suppress pyroptosis in Mtb-infected macrophages. Further study also demonstrated that siNrf2 could attenuate the inhibitory effect of Andro on TXNIP, validating our mechanistic studies. Thus, our data suggest that Andro may be a potential candidate adjuvant drug for anti-TB therapy as it inhibits pyroptosis in Mtb-infected macrophages, potentially improving clinical outcomes.

Vascular cognitive impairment (VCI) is the second most common form of dementia. Andrographolide (Andro) shows potential effects in anti-inflammation, anti-oxidative stress, and anti-apoptosis. We have obtained 48 potential genes related to the effect of Andro on VCI through network pharmacology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to reveal significant enriched pathway of potential genes, and the mitogen-activated protein kinase (MAPK) pathway was screened out. To verify the results of network pharmacology, we tested the effects of Andro in VCI model induced by bilateral common carotid artery occlusion (BCCAO) surgery. The results showed that Andro treatment ameliorated the cognitive impairment induced by BCCAO. Immunohistochemistry study revealed that Andro could reduce neuronal damage and activation of microglia in the cortex and hippocampus in BCCAO rats. To test the MAPK pathway changes, we analyzed the expression of JNK, p38 and ERK and found that Andro reduced the levels of phosphorylated-ERK (p-ERK) and phosphorylated-p38 (p-p38) in BCCAO rats. In conclusion, Andro could improve neuronal survival, reduce neuroinflammation and ameliorate cognitive impairment in VCI. The underlying mechanisms of Andro treatment may be through the inhibition of MAPK pathway.

Andrographolide (Andro), a diterpene of the labdane family extracted from the Asian plant Andrographis paniculata, is neuroprotective against stroke and Alzheimer's disease. However, whether Andro protected the brain against subarachnoid hemorrhage (SAH) was still unknown. Thus, we explored whether Andro attenuated blood-brain barrier (BBB) disruption and neuronal apoptosis and inhibited oxidative stress to protect the brain against SAH both in vitro and in vivo and detected underlying mechanisms of Andro's neuroprotective effects in the present study. Oxyhemoglobin (OxyHb)-treated neuronal PC12 cells were used as an in vitro model. An in vivo model was established using Sprague-Dawley rats. Moreover, we used an inhibitor of heme oxygenase-1 (HO-1) (ZnPPIX) in vitro and in vivo experiments to evaluate whether the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade acted as one protective molecular mechanism of Andro against SAH. Our results revealed that, in vitro, Andro increased cell viability, inhibited apoptosis, and activated Nrf2/HO-1 cascade of neuronal PC12 cells treated with OxyHb. In vivo, Andro attenuated the neurological dysfunction, neuronal apoptosis, BBB disruption, brain edema, and oxidative stress and activated the Nrf2/HO-1 pathway. ZnPPIX reversed the effects of Andro in vitro and in vivo. Our research suggested that Andro alleviated BBB disruption, neuronal apoptosis, and oxidative stress in SAH, possibly via the Nrf2/HO-1 signaling pathway.

Metabolic syndrome (MetS) and andrological diseases share common risk factors and common patho-physiological mechanism. In this brief review we describe the relation between metabolic syndrome and male sexual disorders, and we explore the available evidence of the pathophysiological mechanisms correlating these conditions. The aim of this study was to describe the relation between metabolic syndrome and andrological diseases. Current literature shows strong evidence on the association between pathophysiological mechanisms linking metabolic syndrome and andro-urological diseases, such as premature ejaculation, erectile dysfunction, and hypogonadism. Strong associations are seen between male sexual dysfunction and central obesity, poor glycemic control, hyperlipidemia, as well as hypertension. The constellation of risk factors leading to metabolic syndrome are linked to male sexual dysfunction and are largely modifiable. Therefore, effective interventions targeting the underlying pathophysiology have the potential to greatly impact and improve patient sexual function and, ultimately, quality of life.

Andrographolide (ANDRO), a bitter diterpene lactone found in Andrographis paniculata (Burm.f.) Nees, possesses several biological effects such as antioxidant, anti-inflammatory, and organo-protective effects. Scientific reports suggest that it also has neuroprotective capacity in various test systems. The purpose of this review was to synthesize the neuropharmacological properties of ANDRO and highlight the molecular mechanisms of action that highlight these activities. A careful search was done in PubMed and Google Scholar databases using specific keywords. Findings suggest that ANDRO possess neuroprotective, analgesic, and antifatigue effects. Prominent effects were stated on neuro-inflammation, cerebral ischemia, Alzheimer's and Parkinson's diseases, multiple sclerosis, and brain cancer in mice and rats. Furthermore, ANDRO and its derivatives can enhance memory and learning capacity in experimental animals (rats) without causing any toxicity in the brain. Thus, ANDRO may be one of the most promising plant-based psychopharmacological lead compounds for new drug development.