Detoxification and underlying mechanisms towards toxic alkaloids by Traditional Chinese Medicine processing: A comprehensive review.

BACKGROUND: Alkaloids have attracted enduring interest worldwide due to their remarkable therapeutic effects, including analgesic, anti-inflammatory, and anti-tumor properties, thus offering a rich source for lead compound design and new drug discovery. However, some of these alkaloids possess intrinsic toxicity. Processing (Paozhi) is a pre-treatment step before the application of herbal medicines in traditional Chinese medicine (TCM) clinics, which has been employed for centuries to mitigate the toxicity of alkaloid-rich TCMs. PURPOSE: To explore the toxicity phenotypes, chemical basis, mode of action, detoxification processing methods, and underlying mechanisms, we can gain crucial insights into the safe and rational use of these toxic alkaloid-rich herbs. Such insights have the great potential to offer new strategies for drug discovery and development, ultimately improving the quality of life for millions of people. METHODS: Literatures published or early accessed until December 31, 2023, were retrieved from databases including PubMed, Web of Science, and CNKI. The following keywords, such as "toxicity", "alkaloid", "detoxification", "processing", "traditional Chinese medicine", "medicinal plant", and "plant", were used in combination or separately for screening. RESULTS: Toxicity of alkaloids in TCM includes hepatotoxicity, nephrotoxicity, neurotoxicity, cardiotoxicity, and other forms of toxicity, primarily induced by pyrrolizidines, quinolizidines, isoquinolines, indoles, pyridines, terpenoids, and amines. Factors such as whether the toxic-alkaloid enriched part is limited or heat-sensitive, and whether toxic alkaloids are also therapeutic components, are critical for choosing appropriate detoxification processing methods. Mechanisms of alkaloid detoxification includes physical removal, chemical decomposition or transformation, as well as biological modifications. CONCLUSION: Through this exploration, we review toxic alkaloids and the mechanisms underlying their toxicity, discuss methods to reduce toxicity, and unravel the intricate mechanisms behind detoxification. These offers insights into the quality control of herbs containing toxic alkaloids, safe and rational use of alkaloid-rich TCMs in clinics, new strategies for drug discovery and development, and ultimately helping improve the quality of life for millions of people.

Relationship Between Autonomic Nervous System Activity and Axial Length in Children.

BACKGROUND The aim of this work was to compare autonomic nervous system activity between eyes with axial and non-axial myopia and to investigate the relationship between autonomic nervous system activity and axial length (AL) in children. MATERIAL AND METHODS Seventy-eight eyes of 78 children were included in this study. Static and dynamic pupillary responses, including pupil diameter, latency, and velocity of pupil contraction and dilation, were recorded using automatic pupillometry to evaluate autonomic nervous system activity. AL was measured using the IOL-Master device. RESULTS In terms of static pupillary responses, the pupil diameter at mesopic condition (1 candelas/m²) (PD1) (4.06±0.64 vs 3.80±0.87 mm, P=0.045) and pupil diameter at low photopic condition (10 candelas/m²) (PD10) (3.40±0.49 vs 3.22±0.66 mm, P=0.046) were significantly larger in axial myopic eyes than in non-axial myopic eyes. In terms of dynamic pupillary responses, velocity of pupil contraction (Vel-C) (5.93±0.89 vs 6.75±1.60 mm/s, P=0.019) and velocity of pupil dilation (Vel-D) (2.28±0.38 vs 2.89±1.17 mm/s, P=0.002) were significantly slower in axial myopic eyes than in non-axial myopic eyes. Moreover, PD1 and PD10 were significantly and positively associated with AL, while Vel-C and Vel-D were significantly and negatively associated with AL (all P<0.05). CONCLUSIONS There was significant decrease in autonomic nervous system activity in axial myopia compared with non-axial myopia, and autonomic nervous system activity was significantly and negatively associated with AL in children. Decreases in autonomic nervous system activity in axial myopia may contribute to the excessive axial elongation in pediatric axial myopia.

Quantitative analysis of internal components of the human crystalline lens during accommodation in adults.

To quantitatively analyze changes in the inner components of the human crystalline lens during accommodation in adults. Eyes of 23 subjects were sequentially examined using CASIA2 Optical Coherence Tomography under 0D, - 3D and - 6D accommodation states. The anterior chamber depth (ACD), anterior and posterior crystalline lens radius of the curvature (ALRC and PLRC) were obtained using built-in software. The lens thickness (LT), lenticular nucleus thickness (NT), anterior cortex thickness (ACT), posterior cortex thickness (PCT), anterior and posterior lenticular nucleus radius of the curvature (ANRC and PNRC), anterior and posterior lenticular nucleus vertex (ANV and PNV) were quantified manually with the Image-pro plus software. During accommodation, the ACD became significantly shallower and LT significantly increased. For changes in the lens, the ALRC decreased by an average magnitude (related to accommodative stimuli) 0.44 mm/D, and PLRC decreased 0.09 mm/D. There was no difference for the ACT and PCT in different accommodation states. For lenticular nucleus response, NT increased on average by 30 µm/D. Both the ANRC and PNRC decreased on average by 212 µm/D and 115 µm/D respectively. The ANV moved forward on average by 0.07 mm under - 3D accommodative stimuli and 0.16 mm for - 6D. However, there was no statistically significant difference between different accommodation states in the PNV movement. Under accommodation stimulation, lens thickness changed mainly due to the lenticular nucleus, but not the cortex. For the lenticular nucleus, both the ANRC and PNRC decreased and ANRC changed the most. The anterior surface of the nucleus moved forward while the posterior surface of the nucleus moved backward but only slightly.

Acute Effects of Intraocular Pressure-Induced Changes in Schlemm's Canal Morphology on Outflow Facility in Healthy Human Eyes.

Purpose: To estimate the outflow facility coefficient (C) as a function of Schlemm's canal cross-sectional area (SCAR) in healthy subjects using noninvasive oculopression tonometry (OPT). Methods: In 25 healthy volunteers, intraocular pressure (IOP) decay values were recorded by a ophthalmodynamometer, with a fixed external force (0.15 N) on the inferior-temporal eyelid, every 10 seconds, for four minutes, and again after a 30-minute rest. Schlemm's canal profile images and IOP were obtained pre-procedurally (baseline), immediately (T0), and at 1-minute intervals post-procedurally (T1, T2, T3, and T4). C was calculated for different IOPs. The SCAR, coronal, and the meridional diameter of Schlemm's canal were calculated. Results: Mean C0 for the maximum IOP was 0.020 ± 0.017 µL/min/mm Hg; mean C was 0.018 ± 0.0071 and 0.058 ± 0.0146 µL/min/mm Hg at 40 and 20 mm Hg, respectively. C was nonlinearly dependent on the IOP (R2 = 0.945). The SCAR was 5440 ± 3140.82, 3947.6 ± 2246.8, and 5375.7 ± 2662.7 µm2 at baseline, T0, and T4, respectively. The coronal diameter of SC decreased significantly from the baseline (33.02 ± 11.3 µm) to T0 (26.6 ± 9.37 µm) and recovered at T4 (32.3 ± 9.53 µm). The SCAR and IOP correlated significantly throughout (R2 = 0.9944; P < 0.001). C0 significantly correlated with the SCAR at baseline and with changes in the SCAR and IOP from T0 to T4. Conclusions: Schlemm's canal dimensions are responsible for the IOP-dependent mechanical forces, and these changes appear to directly affect outflow facility.

Dual effect of the Valsalva maneuver on autonomic nervous system activity, intraocular pressure, Schlemm's canal, and iridocorneal angle morphology.

BACKGROUND: The Valsalva maneuver (VM) is widely used in daily life, and has been reported to cause high intraocular pressure (IOP). This study aimed to assess changes in IOP, the Schlemm's canal (SC), autonomic nervous system activity, and iridocorneal angle morphology in healthy individuals during different phases of the VM. METHODS: The high frequency (HF) of heart rate (HR) variability, the ratio of low frequency power (LF) and HF (LF/HF), heart rate (HR), IOP, systolic (SBP) and diastolic blood pressure (DBP), the area of SC (SCAR), pupil diameter (PD), and some iridocorneal angle parameters (AOD500, ARA750, TIA500 and TISA500) were measured in 29 young healthy individuals at baseline, phase 2, and phase 4 of the VM. SBP and DBP were measured to calculate mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP). HF and the LF/HF ratio were recorded using Kubios HR variability premium software to evaluate autonomic nervous system activity. The profiles of the anterior chamber were captured by a Spectralis optical coherence tomography device (anterior segment module). RESULTS: Compared with baseline values, in phase 2 of the VM, HR, LF/HF, IOP (15.1 ± 2.7 vs. 18.8 ± 3.5 mmHg, P < 0.001), SCAR (mean) (7712.112 ± 2992.14 vs. 8921.12 ± 4482.79 µm2, P = 0.039), and PD increased significantly, whereas MOPP, AOD500, TIA500, and TISA500 decreased significantly. In phase 4, DBP, MAP, AOD500, ARA750, TIA500and TISA500 were significantly lower than baseline value, while PD and HF were remarkably larger than baseline. The comparison between phase 2 and phase 4 showed that HR, IOP (18.8 ± 3.5 vs. 14.7 ± 2.9 mmHg, P < 0.001) and PD decreased significantly from phase 2 to phase 4, but there were no significant differences in other parameters. CONCLUSIONS: The expansion and collapse of the SC in different phases of the VM may arise from changes in autonomic nervous system activity. Further, the effects of the VM on IOP may be attributed to changes in blood flow and ocular anatomy. TRIAL REGISTRATION: This observational study was approved by the ethics committee of Tongji Hospital (Registration Number: ChiCTR-OON-16007850, Date: 01.28.2016).

The impact of transgenic wheat expressing GNA (snowdrop lectin) on the aphids Sitobion avenae, Schizaphis graminum, and Rhopalosiphum padi.

This study investigated the impact of transgenic wheat expressing Galanthus nivalis agglutinin (GNA), commonly known as snowdrop lectin, on three wheat aphids: Sitobion avenae (F.), Schizaphis graminum (Rondani), and Rhopalosiphum padi (L.). We compared the feeding behavior and the life-table parameters of aphids reared on GNA transgenic wheat (test group) and those aphids reared on untransformed wheat (control group). The results showed that the feeding behaviors of S. avenae and S. graminum on GNA transgenic wheat were affected. Compared with the control group, they had shorter initial probing period, longer total nonprobing period, shorter initial and total phloem sap ingestion phase (waveform E2), shorter duration of sustained ingestion (E (pd) > 10 min), and lower percentage of phloem phase of the total observation time. Moreover, S. graminum made more probes and had a longer total duration of extracellular stylet pathway (waveform C). The fecundity and intrinsic rate of natural increase (r(m)) of S. avenae and S. graminum on the transgenic wheat were lowered in the first and second generations, however, the survival and lifespan were not affected. The effects of the GNA expressing wheat on S. graminum and S. avenae were not significant in the third generation, suggesting rapid adaptation by the two aphid species. Despite the impact we found on S. avenae and S. graminum, transgenic GNA expressing wheat did not have any effects on R. padi.