The processing methods, phytochemistry and pharmacology of Gastrodia elata Bl.: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Bl. (GE) is one of the rare Chinese medicinal materials with a long history of medicine and cooking. It consists of a variety of chemical components, including aromatic compounds, organic acids and esters, steroids, saccharides and their glycosides, etc., which has medicinal and edible value, and is widely used in various diseases, such as infantile convulsions, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. It is also commonly used in health care products and cosmetics. Thus, its chemical composition and pharmacological activity have attracted more and more attention from the scientific community. AIM: In this review, the processing methods, phytochemistry and pharmacological activities of GE were comprehensively and systematically summarized, which provides a valuable reference for researchers the rational of GE. MATERIALS AND METHODS: A comprehensive search of published literature and classic books from 1958 to 2023 was conducted using online bibliographic databases PubMed, Google Scholar, ACS, Science Direct Database, CNKI and others to identify original research related to GE, its processing methods, active ingredients and pharmacological activities. RESULTS: GE is traditionally used to treat infantile convulsion, epilepsy, tetanus, headache, dizziness, limb numbness, rheumatism and arthralgia. To date, more than 435 chemical constituents were identified from GE including 276 chemical constituents, 72 volatile components and 87 synthetic compounds, which are the primary bioactive compounds. In addition, there are other biological components, such as organic acids and esters, steroids and adenosines. These extracts have nervous system and cardiovascular and cerebrovascular system activities such as sedative-hypnotic, anticonvulsant, antiepileptic, neuron protection and regeneration, analgesia, antidepressant, antihypertensive, antidiabetic, antiplatelet aggregation, anti-inflammatory, etc. CONCLUSION: This review summarizes the processing methods, chemical composition, pharmacological activities, and molecular mechanism of GE over the last 66 years, which provides a valuable reference for researchers to understand its research status and applications.

[Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy].

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Systematic review and Meta-analysis of efficacy and safety of Tangmaikang Granules in treatment of diabetic peripheral neuropathy / 中国中药杂志

This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PURPOSE: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2 O) abuse, and analyze the factors that affect outcomes. METHODS: Patients with N2 O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow-up was conducted to determine the outcomes. RESULTS: The average age of the 110 patients with N2 O abuse was 21.4 ± 4.2 years (range: 14-33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2 O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow-up was completed for 51 patients. Thirty-four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients. CONCLUSION: The recreational use of N2 O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2 O abuse. The therapeutic administration of vitamin B12 supplementation and N2 O withdrawal can make the overall prognosis good, especially for female patients.

Vitamin B12 Deficiency Anemia and Polyneuropathy Due to Chronic Radiation Enteritis.

A 62-year-old Japanese woman developed numbness of the extremities and megaloblastic anemia. She had undergone total abdominal hysterectomy, whole-pelvis radiation therapy and chemotherapy for gynecological cancer 10 years before. Chronic abdominal pain, diarrhea and intermittent small-bowel obstruction had afflicted her for a long time. We diagnosed her with vitamin B12 deficiency anemia and polyneuropathy due to chronic radiation enteritis causing malabsorption. Vitamin B12 injections improved her numbness and anemia. The early diagnosis and treatment of deficiency of vitamin B12 are important. Physicians should regularly measure vitamin B12 levels and supplement vitamin B12 as needed in patients with chronic radiation enteritis.

Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats.

Oxaliplatin, a widely used chemotherapeutic agent, induces peripheral neuropathy that manifests itself as two distinct phases: acute cold hyperesthesia and chronic peripheral hypoesthesia/dysesthesia. The latter is a serious dose-limiting side effect that can often lead to withdrawal of treatment. We have developed a rat model expressing both phases and used the model to investigate the action of goshajinkigan (GJG), a traditional Japanese herbal medicine, which was reported to ameliorate oxaliplatin-induced neuropathy in a placebo-controlled double-blind randomized phase II study. In this study, neuropathy was induced by injection of oxaliplatin twice weekly for 8 wks. The maximum level of cold hyperesthesia was observed at 4 wks with heat hypoesthesia developing later. Microscopy studies revealed atrophy of axons of myelinated sciatic nerve fibers in oxaliplatin-treated rats at 8 wks. Co-administration of GJG ameliorated both abnormal sensations as well as histological damage to the sciatic nerve. A pharmacokinetic study revealed numerous neuroprotective components of GJG that are rapidly absorbed into the blood. GJG and some of its components attenuated the generation of oxaliplatin-induced reactive oxygen species, which is a possible mechanism of oxaliplatin-induced neurotoxicity. The present study provides a useful animal model for oxaliplatin-induced neurotoxicity as well as a promising prophylactic agent.

Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats.

The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

[Basic knowledge about Kampo for neurologists].

Kampo is a traditional form of medicine in Japan. The individual formulas of the Kampo medicines consist mainly of plant-derived crude drugs. Recently, extract products that maintain specific levels of quality have been commonly used for dosage formulation instead of decoction. Although severe side effects, including pseudoaldosteronism, interstitial pneumonitis, liver damage and mesenteric phlebosclerosis may occasionally arise in some patients, herbal formulations are generally safe compared with potent western medicines. Since the complicated interaction of a Kampo formulation is difficult to analyze pharmacologically, the use of each Kampo formula has been based on the empirical rules described in classical writings by clinicians. Currently, formula selection is not always based on the pathological recognition from the Oriental medicine perspective, because these ancient theories are not necessarily amenable to current clinical practice. Nevertheless, formula selection would be more appropriate, and the therapeutic efficacy would increase if the physicians understood the basic concepts of ki, ketsu, sui, yin-yang, hypofunction and hyperfunction, heat and cold, superficies and interior, the five parenchymatous viscera and the six stages of disease. Regardless of the primary diseases, many Kampo formulas are considered to be indicated for patients complaining of headache, dizziness and numbness, which are common symptoms in everyday practice in neurology.

Phentolamine mesylate for accelerating recovery from lip and tongue anesthesia.

Phentolamine mesylate, at dosages from 0.4 to 0.8 mg in adults and adolescents and at dosages from 0.2 to 0.4 mg in children aged 4 to 11 years, has been proven to be safe and effective for the reversal of soft tissue anesthesia (lip and tongue numbness) and the associated functional deficits resulting from a local dental anesthetic injection containing a vasoconstrictor. Its ability to block a-adrenergic receptors on blood vessels induces vasodilation and enhances the redistribution of the local anesthetic away from the injection site. The low dosages administered for dental local anesthetic reversal in all likelihood accounts for the lack of significant cardiovascular effects that are associated with the medical use of the drug for hypertensive conditions associated with catecholamine excess.

The effect of Rexflavone (Sophorae fructus extract) on menopausal symptoms in postmenopausal women: a randomized double-blind placebo controlled clinical trial.

To observe the protective effect of orally administrated Rexflavone (Sophorae fructus extract) for the postmenopausal symptoms, a randomized double-blind placebo controlled clinical trial was designed. Rexflavone significantly improved 11 menopausal symptoms including hot flash, which was evaluated by the modified Kupperman Index (KI), while hormone level and lipid profile were little changed by consumption. Rexflavone group significantly decreased KI score (-14.91 +/- 8.79) compared to placebo group (-11.45 +/- 6.62) as a representative index for improvement of menopausal symptoms (p < 0.05). We found that Rexflavone has no adverse effect to be safe for long term consumption. It was shown that the consumption of Rexflavone possessed beneficial effects on the postmenopausal symptoms in postmenopausal women.

Efficacy of keishibukuryogan, a traditional Japanese herbal medicine, in treating cold sensation and numbness after stroke: clinical improvement and skin temperature normalization in 22 stroke patients.

Cold sensation and numbness have been reported as post-stroke sensory sequelae attributable to distal axonopathy, which is caused by chronic ischemia of diseased limbs resulting from dysfunction of vasomotor regulatory systems. Keishibukuryogan is a traditional herbal medicine used to treat symptoms of peripheral ischemia such as cold extremities. This study investigated clinical improvement and skin temperature in peripheral ischemia patients to determine the efficacy of keishibukuryogan in alleviating post-stroke cold sensation and numbness. Twenty-two stroke patients with cold sensation and/or numbness were enrolled in this study. Subjective cold sensation and numbness, evaluated using the visual analogue scale, were found in 21 and 31 limbs, respectively. The skin temperature of diseased and healthy limbs was recorded. We observed all patients for 4 weeks and 17 patients for 8 weeks after administration of keishibukuryogan. The skin temperature of diseased limbs was significantly higher than baseline at 4 weeks and 8 weeks, whereas that of healthy limbs did not change significantly. Cold sensation and numbness were significantly improved at 4 weeks and 8 weeks compared to baseline. Keishibukuryogan administration resulted in warming of diseased limbs and improved cold sensation and numbness, probably by increasing peripheral blood flow.

[Observation on therapeutic effect of digital acupoint pressure for treatment of the nerve root type of cervical spondylosis].

OBJECTIVE: To observe the therapeutic effect of digital acupoint pressure for treatment of the nerve root type of cervical spondylosis. METHODS: Four hundred cases were randomly divided into a digital acupoint pressure group (DAP group) and a medicine group, 200 cases in each group. Acupoints of Quepen (ST 12), Jianjing (GB 21) and Tianzong (ST 11) etc. were used for digital pressing in the DAP group; and Chinese herb medicine of Gentongping was routinely taken in the medicine group. After three treatment courses, the symptoms of pain and numbness, the signs of pressure measurement by compression of head, brachial plexus drawer test and arm myodynamia, as well as the total cumulative scores of daily living capability, were compared. RESULTS: After treatment, the total cumulative scores of numbness, pressure measurement by compression of head, brachial plexus drawer test, arm myodynamia and daily living capability in both groups were obviously better than those of before treatment (all P<0.01); but there was a significant difference on the total cumulative score of the symptoms and signs between the two groups. The cured rate of 78.0% and total effective rate of 99.0% in the DAP group were better than those of 61.0% and 87.0% in the medicine group, respectively (both P<0.01). CONCLUSION: Digital acupoint pressure plays an active role in improving the symptoms and signs on patients with nerve root type of cervical spondylosis, which is better than Chinese herb medicine of Gentongping.

[Isoniazid induced neuropathy: consider prevention]. / Neuropathie toxique induite par l'isoniazide: pensez à la prévention.

INTRODUCTION: Antituberculous treatment is effective but has numerous side effects. Among these isoniazid induced neuropathy is easily preventable. CASE REPORT: A female patient of 42 years, infected with HIV, presented with general deterioration associated with an interstitial pulmonary infiltrate and mediastinal lymphadenopathy. Tuberculosis was not confirmed bacteriologically but she responded to antituberculous treatment. Three months later she developed distal leg pains extending proximally. There was superficial sensory impairment up to the groins and loss of the ankle reflexes. The dose of isoniazid was reduced from 5 to 2.5 mg/kg/day on account of slow acetylator status and treatment with pyridoxine 250 mg/day commenced. The clinical signs resolved in a few weeks. CONCLUSIONS: Isoniazid neuropathy develops in the presence of risk factors (HIV, alcoholism, diabetes, renal failure, malnutrition, pregnancy and lactation, neurotoxic medication) and manifests itself initially by burning feet. Pyridoxine is preventative in low dosage and curative in high dosage. The development of symptoms should lead to measurement of acetylator status, and a reduction of the isoniazid dose to 3 mg/kg/day or even less in slow acetylators.