Parkinson and Hypericum perforatum: a medical hypothesis

Parkinson's disease (PD) is a common neurological disorder that is defined by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta, eventually leading to striatal dopamine depletion.Resting tremors, rigid muscles, bradykinesia, and in rare circumstances, postural instability are symptoms of low dopamine levels.One to two percent of people over 65 worldwide is affected with PD, making it the second most common neurological illness in the world [1, 2].Uncertainty about the cause and course of PD persists, as do the biological pathways that drive the disease [3].

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial PD [4].LRRK2 missense mutations increase the risk of developing late-onset autosomal dominant PD,which is clinically comparable to sporadic PD [5, 6].LRRK2 PD neuropathology is comparable to sporadic PD neuropathology, with LRRK2 patients experiencing progressive neurodegeneration of the nigrostriatal pathway, frequently resulting in alpha-Synuclein-positive Lewy bodies and brain tau pathology [5, 7–9].While LRRK2 coding mutations are associated with sporadic PD, frequent non-coding variants at the LRRK2 locus are associated with an increased risk of developing PD [10–13].

LRRK2 and Glycogen synthase kinase-3 beta (GSK-3β) are two such kinases that have been directly linked to the production of tau and alpha-Synuclein proteins, which cause PD [14].Dysregulation of GSK-3 affects the central nervous system and leads to neurodegenerative and neuroinflammation diseases.GSK-3β is one of its isomers having an effective role in neuronal apoptosis [15].

2.1 子宫内膜组织中ER、PR的表达水平 所有患者子宫内膜均有不同程度ER、PR的表达，腺体中ER阳性率为66.2%，PR阳性率为58.1 %；内膜间质中ER阳性率为42.6%，PR阳性率为36.0%，有统计学意义(P<0.05)。见表2。

These results indicate that in addition to causing neuropathology in familial PD, LRRK2 contributes to pathways implicated in sporadic PD.As a result, inhibiting LRRK2-dependent molecular pathways is a potential strategy for discovering new treatment goals for familial and sporadic PD.

Seung-Hwan Kwon and colleagues showed that hyperoside shields cultured dopaminergic neurons from death through reactive oxygen species-dependent processes, that hyperoside also has neuroprotective impacts on 6-OHDA-induced neurotoxicity in neurons, as well as the potential underlying systems.Hyperoside substantially reduced neuronal cell viability loss, lactate dehydrogenase release,uncontrolled reactive oxygen species buildup, and mitochondrial membrane potential malfunction linked to 6-OHDA-induced neurotoxicity.Additionally, hyperoside therapy activated the nuclear erythroid 2-related factor 2 (Nrf2), a molecule upstream of heme oxygenase-1.Hyperoside also increased the levels of the antioxidant response gene heme oxygenase-1 (HO-1).The neuroprotective benefits of hyperoside were reduced by an Nrf2 small interfering RNA, which inhibited hyperoside's capacity to prevent neuronal death,demonstrating the importance of HO-1.Altogether, hyperoside inhibits neuronal death induced by 6-OHDA-induced oxidative stress via inducing Nrf2-dependent HO-1 activation.Furthermore,Nrf2-dependent HO-1 signaling activation is a potential preventative and curative purpose in PD treatment [28].

Treatments for PD patients are currently available; however, they do not prevent the disease from progressing [1, 2].Alternative and complementary therapies for PD have been shown to be effective in delaying the onset of the disease and alleviating its symptoms [16].Natural products continue to be a promising source of biochemical specificity, chemical variety, and various molecular properties,making them well-suited for modulating many signaling cascades/pathways in various clinical states, such as cancer and neurological illnesses [17].

Hesperidin is a flavanone glycoside that possesses many therapeutic qualities, most notably neuroprotective properties [14].Hesperidin significantly protected SH-SY5Y (ATCC CRL-2266) cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo by downregulating oxidative stress indicators and also by downregulating the kinases GSK-3 β and LRRK2 as well as polg, casp3,and casp9 [14].

According to studies,

extracts contain extremely high hesperidin, hyperoside, and quercetin [20].

extracts have been demonstrated to be effective in treating mild/moderate depression in numerous studies [21, 22].Anti-cancer, antiviral,neuroprotective, wound healing, and antioxidant are some of the other key pharmacological features of

[23–27] (Figure 1).

L.(Hypericaceae) commonly referred to as St.John's wort, is one of the most important and widespread species in the

genus.Because

extracts have no notable harmful effects on humans or animals, their use has expanded dramatically during the last decade [18].

is recognized as one of the greatest herbs available today due to its established market position, appeal, and efficacy.

formulations are sold in numerous countries as nutritional supplements,antidepressants, mood enhancers, and relaxants [19].

【12】汤显祖《牡丹亭记题词》，见《牡丹亭记题词》，见徐朔方笺校《汤显祖全集》，北京古籍出版社1999年版，第1153页。

例4 (2018年株洲中考卷)如图9，O为坐标原点，△OAB是等腰直角三角形，∠OAB=90°，点B的坐标为将该三角形沿x轴向右平移得到Rt△O′A′B′，此时点B′的坐标为则线段OA在平移过程中扫过部分的图形面积为________.

Quercetin is a potent flavonoid having anti-inflammatory,antioxidant, and anti-cancer properties [29].According to studies,quercetin may protect against hyperphosphorylation of tau protein and oxidative stress caused by Okadaic acid [29].Additionally, oral quercetin therapy significantly improves behavioral deficits, striatal dopamine deficiency, and TH neuronal cell loss in MitoPark transgenic mice with progressive dopaminergic neurodegeneration [30].

According to the studies cited,

may be a beneficial and abundant source for limiting PD progression.Thus,

is recommended for further experimental and clinical investigation in PD.

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