CN106963754A - Cyanidenon and the like is used for the purposes for adjusting biological rhythm - Google Patents

Cyanidenon and the like is used for the purposes for adjusting biological rhythm Download PDF

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CN106963754A
CN106963754A CN201710085408.7A CN201710085408A CN106963754A CN 106963754 A CN106963754 A CN 106963754A CN 201710085408 A CN201710085408 A CN 201710085408A CN 106963754 A CN106963754 A CN 106963754A
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change
cyanidenon
biological rhythm
rhythm
disorderly
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CN106963754B (en
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曲丽娜
李莹辉
陈海龙
吕柯
冀国华
曹宏卿
阚广捍
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Space Institute Of Southern China (shenzhen)
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin

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  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The application, which is related to cyanidenon or its analog, is used to preparing the medicine of regulation body biological rhythm or the purposes of health products, and the similar thing of the cyanidenon is selected from apiolin, Kaempferol, Quercetin, myricetin, Isorhamnetin and its glucosides, and combinations thereof.Such compound can be used for regulation biological rhythm, got jet lag including normally illumination round the clock, needs of often going on business, long-term work in shifts, long-term overwork, the overtime work of long-term night, the high complexity work of long campaigns, be chronically at the body biological rhythm occurred when unsafe environment (such as police, miner, fireman) change or it is disorderly and/or by biological rhythm change or it is disorderly caused by body function change, the change of such as body temperature and heart rate, dyssomnias, liver function change or diabetes disease.

Description

Cyanidenon and the like is used for the purposes for adjusting biological rhythm
Technical field
The application belongs to the field of Chinese medicines, and in particular to cyanidenon or its analog are used to prepare regulation body biological rhythm Medicine or health products purposes.
Background technology
Biological rhythm is that body is shown on a variety of varying levels such as molecule, cell, organ, system and behavior By certain time order, the vital activity phenomenon gone round and begun again.Be present rhythmicity in various physiological activities, such as body temperature, heart rate, sleep Dormancy, breathing, immune response, hormone secretion, behavior, cognitive function etc..Biological rhythm disorder can influence sleep, or even high blood occur The mental disease such as the physical diseases such as pressure, diabetes, obesity, apoplexy and depression, anxiety disorder.
In human spaceflight operation, body faces various space environment factors, such as weightless, closed narrow and small environment, noise, light According to changing and radiation etc., wherein the weightless and closed narrow and small environment duration is most long, the influence to body is most extensive, and effect is held The continuous time is also most permanent.Research shows that the experiment such as human body head-down bed-rest of simulated weightlessness, and simulation space flight are closed narrow The experiment of subenvironment such as Mars -500 is tested, and can influence the stable state of body biological rhythm.Biological rhythm changes under space environment Change can cause sleep disordered or insomnia, operational capacity and alertness to reduce, so as to influence health and the work of spacefarer.
In addition, current people generally work big with life stress, daily life is irregular, is highly vulnerable to breakage the biological section of body Rule.Long-term overwork gets jet lag as often gone on business, the overtime work of long-term night, the highly complex work of long campaigns, long-term place In unsafe environment such as police, miner, fireman, when long-term work in shifts, it is easy to cause the biological section of body Rule is disorderly as sleep disordered.In addition, under many pathological conditions, when such as suffering from diabetes, biological rhythm also changes.
Cyanidenon (Lut) is a kind of polyhydroxy chromocor compound, its analog such as apiolin (3,5,7,3 ', 4 '-penta hydroxy group is yellow for (5,7,4 '-trihydroxyflavone), Kaempferol (3,5,7,4 '-kaempferol), Quercetin Ketone), myricetin (3,5,7,3 ', 4 ', 5 '-quercetagetin) and Isorhamnetin (3,5,7,4 '-tetrahydroxy -3 '-methoxyl group is yellow Ketone) etc. be polyhydroxy flavones representative compound.Their structures are similar, are widely present in plant, and with extensive Pharmacological action, such as antioxidation, improve study, memory and effect of nervous functional defects etc..Due to these polyhydroxy flavones Natural origin, toxicologic study and safety evaluatio are respectively provided with it has been shown that their toxic side effect is small, safe-dosaging limits are big.
The content of the invention
Inventor's research finds that cyanidenon and the like can adjust biological rhythm well so that body changes The rhythm and pace of moving things such as heart rate rhythm, body temperature rhythm, sleep rhythm and liver function become or disorderly, body oxidative stress situation etc. are recovered Normally, and their stable state is maintained.
The application provides the medicine or health products of cyanidenon or its analog for preparation regulation body biological rhythm Purposes, wherein the luteolin kind is selected from apiolin, Kaempferol, Quercetin, myricetin, Isorhamnetin and its glucosides like thing, Or one or more combination in them.
In some embodiments, the body occur biological rhythm change or it is disorderly and/or changed by biological rhythm or Body function changes caused by disorderly.Including, such as normal illumination round the clock, often go on business get jet lag, long-term work in shifts, for a long time Overwork, the overtime work of long-term night, the high complexity of long campaigns work, are chronically at unsafe environment (such as police, ore deposit Work, fireman) when the body biological rhythm that occurs change or disorderly and/or body function changes, such as body temperature and heart rate Change, sleep disordered, liver function changes or the disease such as diabetes.
In some embodiments, the medicine or health products are orally or parenterally given.The stomach External square type includes intravenous injection, intramuscular injection, intraperitoneal injection, intraperitoneal injection, hypodermic injection and venoclysis.
In some embodiments, cyanidenon or derivatives thereof can be with pharmaceutically acceptable excipient according to conventional side Pharmaceutically suitable preparation is made in method, such as can be made into tablet, capsule, granule, injection, oral liquid, supensoid agent, microballoon or Liposome etc..
Brief description of the drawings
In the drawings, the data that ordinate is represented represent with average value ± standard error, wherein n=6.In each accompanying drawing and English abbreviation and symbol used in the following example have following meanings:
BW:Body weight;
h:Hour;
BPM:Heart rate;
U:Unit of activity;
LUT:Cyanidenon;
CON:Control group;
SI:Tail hangs isolation combinational environment group;
SI+LUT25:Tail hangs isolation combinational environment+25mg/kg BW cyanidenon treatment groups;
SI+LUT50:Tail hangs isolation combinational environment+50mg/kg BW cyanidenon treatment groups;
SI+LUT100:Tail hangs isolation combinational environment+100mg/kg BW cyanidenon treatment groups;
* the P compared with CON is represented<0.05;
* represents the P compared with CON<0.01;
# represents the P compared with SI<0.05;
## represents the P compared with SI<0.01;
1W is represented the 1st week;
2W is represented the 2nd week;
SCN:Necleus of hypothalamus,supraoptic.
Fig. 1 shows that cyanidenon hangs the tune of rat heart rate, body temperature and movable day-night change under isolation combinational environment to tail Section is acted on.Figure 1A, 1D and 1G are the entire change of continuous two weeks.7:00~19:00 photo-irradiation treatment, 19:00~7:At 00 dark Reason.
Fig. 2 shows that cyanidenon hangs rat heart rate, body temperature and activity rhythm amplitude and peak under isolation combinational environment to tail It is worth the adjustment effect of phase place change.Fig. 2 D, 2E, 2F are respectively the peak phase change of heart rate, body temperature and activity, are time conversion Numerical value;For example, ordinate represents that the peak value of the physical signs appears in the 20 of one day for 20:00 moment, the table of ordinate 20.5 Show that the peak value of the physical signs appears in the 20 of one day:30 moment.7:00~19:00 photo-irradiation treatment, 19:00~7:At 00 dark Reason.
Fig. 3 shows that cyanidenon hangs rat rhythm and pace of moving things central hypothalamic under isolation combinational environment to tail and regards coker (SCN) oxygen Change stress adjustment effect.
Fig. 4 shows that cyanidenon hangs the adjustment effect of rat blood serum oxidative stress under isolation combinational environment to tail.
Fig. 5 shows that cyanidenon hangs the adjustment effect of rat liver oxidative stress under isolation combinational environment to tail.
Embodiment
The present invention is further illustrated below by embodiment.It should be understood that embodiments of the invention are to be used to illustrate The present invention rather than limitation of the present invention.The simple modification or improvement carried out according to the essence of the present invention to the present invention is belonged to The scope of protection of present invention.
Embodiment cyanidenon hangs rat biological rhythm and the adjustment effect of oxidative stress under isolation combinational environment to tail
In the present embodiment, isolation combinational environment animal model, the change of physical signs under Varying Illumination are hung using tail Change, three angles of peak phase of the amplitude of the physical signs rhythm and pace of moving things, the physical signs rhythm and pace of moving things are adjusted to the biological rhythm of cyanidenon Effect is studied.The physical signs includes heart rate, body temperature and sleep (reflecting by animal activity).The tune of biological rhythm One of section factor is extraneous illumination variation, therefore the change of physical signs can reflect life on the whole under Varying Illumination Manage the change of the index rhythm and pace of moving things.Amplitude refers to the peak value and the difference of valley of physical signs in 24 hours biological rhythm cycles, peak phase Refer in 24 hours biological rhythm cycles corresponding numerical value at the time of where the peak value of physical signs.
First, test material
(1) animal:Male SD rat 30,200 ± 20g of body weight, manufacturer is that Beijing magnificent biotechnology of dimension tonneau has Limit company, credit number is SCXK (capital) 2012-0001.
(2) medicine:Cyanidenon, pale yellow powder, purity is more than 98%, lot number 160603;Manufacturer is upper Hiroad Standing grain medical sci-tech Development Co., Ltd.
(3) equipment:Mini Mitter implanted physiological signal wireless remote-measuring systems, are passed by G2HR E-mitter implanteds Sensor, ER-4000 excite receiver and Vitalview DAS to constitute.Manufacturer is Philips Respironics。
(4) kit:MDA (MDA) detection kit, oxidation resistance (TAC) detection kit, superoxides discrimination Change enzyme (SOD) activity detection kit, glutathione peroxidase (GPx) activity detection kit, catalase (CAT) Activity detection kit, manufacturer is that Bioengineering Research Institute is built up in Nanjing.
2nd, test method
Body weight is 200 ± 5g male SD rat, is randomly divided into 5 groups, every group of 6 animals:
(1) control group:Single cage is raised in common rearging cage (i.e. without glass), while one time a day, gavage gives physiological saline;
(2) tail hangs isolation combinational environment group:Head 30 ° of tail-suspensions of low level and surrounding with frosted glass single cage raise, while often Day gavage gives physiological saline;
(3) tail hangs isolation combinational environment+25mg/kg BW cyanidenon groups:Head 30 ° of tail-suspensions of low level and surrounding with hair Glass single cage is raised, while one time a day, gavage gives 25mg/kg BW cyanidenons;
(4) tail hangs isolation combinational environment+50mg/kg BW cyanidenon groups:Head 30 ° of tail-suspensions of low level and surrounding with hair Glass single cage is raised, while one time a day, gavage gives 50mg/kg BW cyanidenons;
(5) tail hangs isolation combinational environment+100mg/kg BW cyanidenon groups:Head 30 ° of tail-suspensions of low level and surrounding with hair Glass single cage is raised, while one time a day, gavage gives 100mg/kg BW cyanidenons.
The equal belly of each group animal is implanted into the G2HR E- of Mini Mitter implanted physiological signal wireless remote-measuring systems Mitter implantable sensors, connection ER-4000 excites receiver and sets up Vitalview DAS and ER-4000 Excite the connection between receiver.Carry out parameter setting in Vitalview, including sensor number correcting code, excite reception Device numbering, Testing index (heart rate, body temperature, activity), sample frequency (1 time/2 minutes), number of animals and group # etc..Then press Place group is handled every animal.Wherein, using the light of 12h illumination -12h dark cycles (abbreviation 12h Dark-light cycles, LD) According to mode, light application time is 7:00-19:00, interlunation is 19:00-7:00.Click on Vitalview " starting test " choosing , continuous 2 weeks collection hearts rate, body temperature, activity datas.
After data acquisition terminates, anesthetized animal, pluck eyeball and take blood (stand 4h after centrifuging and taking serum), put to death animal, take out Rhythm and pace of moving things central hypothalamic regards coker (SCN) and rhythm and pace of moving things periphery effect device liver.Utilize biochemical reagents box detection SCN, serum and liver Dirty oxidative stress, including lipid peroxidation product MDA (MDA) level, oxidation resistance (TAC), superoxides discrimination Changing enzyme (SOD) activity, (kit detection total number born T-SOD activity and manganese superoxide dismutase Mn-SOD live Property, copper-zinc superoxide dismutase Cu, Zn-SOD activity=T-SOD activity-Mn-SOD activity), glutathione peroxidase (GPx) activity, catalase (CAT) activity, compare the oxidative stress of each group SCN, serum and liver.Utilize biochemical process Detect the index for reflecting liver function in serum, including liver complex functionality index total protein (TP), albumin (ALB), globulin (GLO) and ALB/GLO, hepatic injury index glutamic-pyruvic transaminase (ALT) activity, glutamic-oxalacetic transaminease (AST) activity, AST/ALT, alkalescence Phosphatase (ALP) activity and gamma glutamyl transpeptidase (GGT) activity and secretory liver function index total bilirubin (TBIL).Than Compared with each group liver function.
Utilize Vitalview export heart rate, body temperature and the Activity value and corresponding date and time of every 2 minutes 1 time.Than Heart rate, body temperature, activity under the 12h Dark-light cycles of two weeks continuous compared with each group, the 1st week and the 2nd week, illumination and dark condition.Pass through Biological rhythm analysis software Chronos-Fit extracts the circadian parameters such as amplitude, the peak phase of heart rate, body temperature and activity, compares The amplitude and peak phase of each group heart rate of continuous two weeks, the 1st week and the 2nd week, body temperature and activity.
3rd, result of the test
(1) cyanidenon hangs rat biological rhythm, the adjustment effect of oxidative stress under isolation combinational environment to tail
1st, cyanidenon hangs the regulation of rat heart rate, body temperature and activity under brightness change under isolation combinational environment to tail and made With
Heart rate:Tail hang isolation combinational environment under the 1st week, the 2nd week and continuous two weeks in general, in 12 hours brightness Under circulation, illumination and dark condition, the heart rate of rat has no significant change, and cyanidenon processing also has substantially no effect on heart rate (figure 1A-1C)。
Body temperature:During tail hangs isolation combinational environment 2 weeks, under the conditions of 12 hours Dark-light cycles, at the 2nd week black Observe that body temperature significantly raises (P under dark condition<0.05), and 25mg/kg BW and 50mg/kg BW cyanidenons processing it is reversible Turn this body temperature rise (P<0.05) temperature recovery, is made to the level (Fig. 1 D-1F) of control group.In Fig. 1 D, continuous two weeks Average data shows, 25mg/kg BW cyanidenons treatment groups (SI+LUT25) and 50mg/kg BW cyanidenon treatment groups (SI+ LUT50 tail) can be reversed under illumination and dark condition and hang body temperature rise caused by isolation Combined Processing, compared with SI model groups With significant difference;The body temperature and Normal group of two cyanidenon treatment groups of 25mg/kg BW and 50mg/kg BW (CON) approach, illustrate that two cyanidenon treatment groups make elevated temperature recovery to normal control level.In addition, 100mg/ The processing of kg BW cyanidenons, which also has, to reverse body temperature rise, recovers to the trend of control group level.
Activity:During tail hangs isolation combinational environment 2 weeks, under the conditions of 12 hours Dark-light cycles, activity is unchanged, wood Rhinoceros grass element also has substantially no effect on activities in rats.But under illumination condition, the activity enhancing of SI groups, cyanidenon processing can be significantly inverse Turn this activity enhancing, it is reduced to the level (Fig. 1 G-1I) close to Normal group.
The above results show that the body temperature rise and activity that tail hangs the lower rat of combinational environment brightness change can be reversed in cyanidenon Enhancing, makes them return to normal level.
2nd, cyanidenon hangs rat heart rate, body temperature and activity rhythm amplitude and peak phase under isolation combinational environment to tail and become The adjustment effect of change
Heart rate rhythm:During tail hangs isolation combinational environment 2 weeks, rat heart rate rhythm and pace of moving things amplitude significantly reduces (P within the 1st week< 0.01), the reduction of this heart rate rhythm amplitude can be reversed in the processing of 50 and 100mg/kg BW cyanidenons, makes heart rate rhythm amplitude Raise (P<0.05) (Fig. 2A).It can be seen that in fig. 2,50 and 100mg/kg BW cyanidenons, two treatment group (i.e. SI+ LUT50 and SI+LUT100) make significantly to be raised by the heart rate rhythm amplitude that tail hangs the reduction that isolation combinational environment is caused, and make Heart rate rhythm amplitude is increased to the level close to control group.During tail hangs isolation combinational environment 2 weeks, at the 1st week, the 2nd week And continuous two weeks in general, the peak phase of the rat heart rate rhythm and pace of moving things is without significant changes, and cyanidenon processing is substantially not yet Influence the peak phase (Fig. 2 D) of the rat heart rate rhythm and pace of moving things.
Body temperature rhythm:During tail hangs isolation combinational environment 2 weeks, rat temperature rhythm and pace of moving things amplitude significantly raises (P< 0.01), 25mg/kg BW cyanidenons processing can significantly lower the rise (P of rat temperature rhythm and pace of moving things amplitude<0.05) (Fig. 2 B), makes Body temperature rhythm amplitude recovery is to the level close to control group.During tail hangs isolation combinational environment 2 weeks, the rat temperature rhythm and pace of moving things Peak phase is remarkably decreased (P<0.01), 25mg/kg BW cyanidenons processing can significantly raise the peak value phase of the rat temperature rhythm and pace of moving things Position (P<0.01) (Fig. 2 E), makes peak phase return to the level close to control group.
Activity rhythm:During tail hangs isolation combinational environment 2 weeks, activities in rats rhythm and pace of moving things amplitude changes (figure without obvious 2C).During tail hangs isolation combinational environment 2 weeks, the peak phase of the 1st week activities in rats rhythm and pace of moving things has elevated trend, 25 Hes The peak phase (Fig. 2 F) of the activities in rats rhythm and pace of moving things has been lowered in the processing of 50mg/kg BW cyanidenons.
The above results show, the reversible tail of cyanidenon processing hang the rat heart rate rhythm and pace of moving things under combinational environment, body temperature rhythm and The change of activity rhythm, maintains its stable state.
The circadian rhythm of heart rate changes, and points out heart and angiocarpy to be likely to occur problem, it is possible to can trigger Cardiovascular event.Cyanidenon maintains tail to hang the stable state of the rat heart rate rhythm and pace of moving things under combinational environment, points out cyanidenon to protect the heart Vascular system, prevents the generation of adverse cardiac events or intervenes its development.
Normal body temperature is the necessary condition that body carries out metabolism and vital movement.24 hours of maintenance body temperature are round the clock The rhythm and pace of moving things so that body can preferably adjust the event such as energy storage, energetic supersession round the clock.The imbalance of body temperature rhythm and fat, sugar Urinate the metabolic diseases such as disease related.Cyanidenon maintains tail to hang the stable state of the rat temperature rhythm and pace of moving things under combinational environment, points out reseda Have a stable state for helping maintain organism metabolism, the generation of metabolic disease such as pre- preventing obesity, diabetes or intervene its development.
It is general in animal experiment study that the sleep-wake rhythm and pace of moving things is reflected with the animal activity rhythm and pace of moving things.Sleep rhythm disorder is by giving birth to The rule for managing sleep caused by the disease such as rhythm disorder sleep-disorder and sleep-wake schedule disorder is disorderly.Circadian rhythm is disorderly Unrest sleep-disorder is more common in situations such as jet lag, long-term work in shifts, the overtime work of long-term night and high-speed flight or event, And sleep-wake schedule disorder is more common in insomniac.Cyanidenon maintains tail to hang the steady of the activities in rats rhythm and pace of moving things under combinational environment State, points out cyanidenon to prevent or intervene the feelings such as jet lag, long-term work in shifts, the overtime work of long-term night and high-speed flight Sleep-wake rhythm disorder caused by condition, can intervene insomniac, guide it to enter the normal sleep-wake rhythm and pace of moving things.
3rd, cyanidenon hangs rat rhythm and pace of moving things central hypothalamic under isolation combinational environment to tail and regards coker (SCN) oxidative stress Adjustment effect
After tail hangs isolation combinational environment 2 weeks, rat SCN lipid peroxidation injury mark MDAs (MDA) and antioxygen Change ability (TAC) has no significant change, and cyanidenon processing is also substantially without influence (Fig. 3 A-3B).For antioxidase, tail hang every After 2 weeks from combinational environment, SCN manganese superoxide dismutases (Mn-SOD) activity is significantly raised, at 25mg/kg BW cyanidenons Reason can significantly reverse this rise, and the processing of 50 and 100mg/kg BW cyanidenons also has this elevated trend of reverse.Remaining resists Oxidase active, including total number born (T-SOD), copper-zinc superoxide dismutase (Cu, Zn-SOD), glutathione Peroxidase (GPx), catalase (CAT) the activity equal nothing after tail hangs isolation combinational environment 2 weeks or cyanidenon processing Significant change (Fig. 3 C-3F).
4th, cyanidenon hangs the adjustment effect of rat blood serum oxidative stress under isolation combinational environment to tail
After tail hangs isolation combinational environment 2 weeks, rat blood serum TAC levels change without obvious, but 25mg/kg BW resedas TAC significantly raises (P after element processing<0.01) (Fig. 4 B).Tail hangs isolation combinational environment 2 weeks or cyanidenon processing has substantially no effect on Rat blood serum MDA levels, SOD activity, GPx activity or CAT are active (Fig. 4 A, 4C-4F).
(2) cyanidenon hangs the adjustment effect of Liver Function and liver oxidative stress under isolation combinational environment to tail
1st, cyanidenon hangs the adjustment effect of Liver Function under isolation combinational environment to tail
Liver function is mainly evaluated by hepatic injury, complex functionality and secreting function.Isolation combinational environment is hung in tail 2 weeks Afterwards, rat blood serum hepatic injury index glutamic-pyruvic transaminase (ALT) activity significantly rise (P<0.05), third turn of ammonia of glutamic-oxalacetic transaminease/paddy The ratio between enzyme (AST/ALT) is remarkably decreased, and AST, alkaline phosphatase (ALP), Glutamyl transpeptidase (GGT) activity are without substantially change Change, the processing of 25mg/kg BW cyanidenons can significantly reverse the rising of ALT activity and AST/ALT decline, have substantially no effect on AST Or ALP activity, significantly improve GGT activity.Tail, which hangs isolation combinational environment 2 weeks or cyanidenon processing, does not influence rat blood serum Liver total protein (TP), albumin (ALB), globulin (GLO), ALB/GLO levels or secretory liver function index total bilirubin (TBIL) level (table 1).
The cyanidenon of table 1 hangs the adjustment effect of Liver Function under isolation combinational environment to tail
2nd, cyanidenon hangs the adjustment effect of rat liver oxidative stress under isolation combinational environment to tail
After tail hangs isolation combinational environment 2 weeks, rat blood serum GPx activity significantly rise (P<0.05), 25mg/kg BW wood Rhinoceros grass element processing can significantly reverse the rise (P of GPx activity<0.05) (Fig. 5 E).Tail hangs isolation combinational environment 2 weeks or cyanidenon It is active (Fig. 5 A-5D and 5F) that processing has substantially no effect on MDA contents, TAC levels, SOD or CAT.
Conclusion
Experiment shows above, and under closed isolation combinational environment, daily gavage gives the life that cyanidenon can adjust rat Heart rate, body temperature and the activity of rat, adjust heart rate rhythm, the body temperature section of rat under the thing rhythm and pace of moving things, including regulation Varying Illumination The amplitude and peak phase of rule and activity rhythm, regulation rhythm and pace of moving things central hypothalamic regard coker SCN antioxidases Mn-SOD activity, increase The strong overall oxidation resistance of body, prevents the potential hepatic injury of rhythm and pace of moving things periphery effect device liver, and regulation hepatic antioxidant GPx lives Property, so as to maintain the stable state of body biological rhythm.Cyanidenon and the like can adjust biological rhythm well so that machine Change the or disorderly rhythm and pace of moving things such as heart rate rhythm, body temperature rhythm, sleep rhythm and the liver function and body oxidative stress shape of body Condition etc. recovers normal, so as to maintain the stable state of body biological rhythm.

Claims (7)

1. cyanidenon or its analog are used to prepare the medicine of regulation body biological rhythm or the purposes of health products, wherein described The similar thing of cyanidenon is selected from apiolin, Kaempferol, Quercetin, myricetin, Isorhamnetin and its glucosides, or one kind in them Or a variety of combinations.
2. the purposes described in claim 1, wherein the body biological rhythm change or disorder occurs and/or changed by biological rhythm Become or disorderly caused body function changes.
3. the purposes described in claim 2, wherein the biological rhythm changes or disorderly and/or changed by biological rhythm or disorderly Caused body function changes the change for including body temperature and heart rate, sleep disordered, liver function and changed or diabetes.
4. the purposes described in claim 2, wherein the biological rhythm changes or disorderly and/or changed by biological rhythm or disorderly Caused body function change include normal illumination round the clock, need to get jet lag, work in shifts, overwork, night overtime work, from The high complexity work of thing, the body biological rhythm occurred when unsafe conditions change or disorderly and/or body work( It can change, the change of such as body temperature and heart rate, sleep disordered, liver function change or diabetes disease.
5. the purposes any one of claim 1-4, wherein the medicine or health products are orally or parenterally And give.
6. the purposes described in claim 5, wherein the parenteral modes include intravenous injection, intramuscular injection, intraperitoneal injection, Intraperitoneal injection, hypodermic injection and venoclysis.
7. the purposes any one of claim 1-4, wherein cyanidenon or derivatives thereof are assigned with pharmaceutically acceptable Tablet, capsule, granule, oral liquid, supensoid agent, injection, microballoon or liposome is made in shape agent according to a conventional method.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018127612A3 (en) * 2017-09-13 2018-08-09 Clariant International Ltd Compositions comprising lespedeza plant extract
CN115089575A (en) * 2022-07-15 2022-09-23 杭州电子科技大学 Application of luteolin in preparation of medicine or anti-aging product

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